American Heart Journal(32)

American Heart

Oh. 32

July, 1946

No. 1

Original Communications

FOREIGN BODIES IN AND IN RELATION TO THE THORACIC

BLOOD VESSELS AND HEART

III. Indications for the Removal of Intracardiac Foreign Bodies
AND THE Behavior of the Heart During Manipulation

Lieutenant Colontsl Dwight E. Harken, M.C,, and jM-vjor Paul M. Zoll, M.C,

Arjiy of the United States

A ristotle wrote, ‘'The lieart alone of all viscera cannot withstand serious
injury.”^ At the end of the last eentiny, Stephen Paget- had gained no
'optimism, for he commented, “Surgery of tlie lieart lias probably reached the
limit set by Nature to all surgery : no new method, and no new discovery, can
overcome the natural difficulties tliat attend a wound of the heart,” yet less
than one year later, on Sept. 9, 1896, Rehn,^ in Frankfurt, successfully sutured
i a stab wound of the right ventricle. Within ten years over a hundred such
cases of cardiac suture had been reported, and now several himdred more have
been added, the majority of wliich have been successful.

Elective intracardiac surgery first centered around the removal of foreign
liodies; Decker* reported that there had been at least twenty-four successful
‘ eases by 1939. There will be more when the results of surgery in World War II
( are known.

The brilliant work and writing on heart surgery by Doyan, Duval, Tuffier,
Carrel, Graham, Beck, and Cutler mark the evolution from dreams to experi-
• ment and from experiment to bold human adventure.

Today it is fair to expect certain simple intracardiac maneuvers to be
' .successful. Tbe door lias been opened by modern anesthesia and the technique
of rapid blood replacement.

The purpose of this paper is. twofold: first, to elaborate on- the indications
for surgiciil removal of m-traeardietc foreign- hodves; and second, to describe and

Appreciation is expre.ssed to the Sias Laboratories of
•lass., for their assistance in the j.ublication of this_ article and for the provision of facilities
3r further investigation in cardiac, surgery now being undertaken.

Presented as tbe substance j'f-tbe Joseph Strickland Goodall Memorial Lecture at tbe
ociety of Apothecaries, London, 'o’< ‘June 26, 1945.

Tleceivcd for. publication Sept. 21, 1945.

AMERICAN HEART JOURKAI-

iUuxtralc ihc hchavior of ihc hcari duriny vuinipuUition. The discussion is
based on experience in the removal ol‘ missiles distributed as indicated in Table
I, and is concerned principally Avith the 26 pericardial and 13 intracardiac
missiles. Fig. 1 shows the intracardiac missiles that have been removed. There
are seven from the chamber of the right ventricle, four from the chamber of
the right auricle, one from tlie left auricular cavity, and one from a small cystic
niyoenrdial hernia in the left ventri(;]e.

PWlCS

i.Kf'.’TT kz Trr leoe* on cjja

4bfe«fi tn

4

%

W

eliar!>«r 4
Mil

122 «c«i:‘‘La

trrr ffpr»:cL»

Fit;. 1- — Intracardiac foreign botVios that have been removed.

T.Miia; 1. DiSTiauuTiox or 134 Missiles ix Eel.\tiox to the Peiucaudium, Heart, and

Gre.vt Vessels

Pericardial 2C

Involving pericardium but iirincipaliy pulmonary 17

Intracardiac ' 13

On great vessels (and in walls) 3:j

Intravascular (three embolic) 7

On great vessels but principally pulmonary 17

lilcdiastinal but not directly on great vessels 19

Total ~~ ~ 134

Heaths 0

INDICATIONS FOR HEMOVAE OF INTRACARDIAC FOREIGN BODIES

The tir.st jiart of tliis discussion pertains to the indications for the removal
of intracardiac foreign bodies.

Tlie pre.ssnre of tvork during the jiast year has been sucli that there was
little time for review of the medical literature. When .such consultation was
sought it was usually disaiiiiointing. Often it has been difficult to acce]H re-
ported foreign bodies as '‘in ihc heart'' when tliorc has been no confirmation
of the location hy autopsy or .surgical exploration. Even surgical exploration
may In- uncertain in the iire.senee of an infected hematoma williin the peri-
eardhim nr auricle. In short, it is probable that some of tlie reported “intra-
cartliiie” missiios were not in ihc heart.

IIAKKEN AND ZOf.I. : PORKICX BODIES IX UEABT

o

tJ

Persona] experience confirined the difficnlty of aecnrate localization of
metallic fragments in relation to the Jieart. Almost one-half of the foreign
bodies referred to us as “in the Jieart were found by careful fluoroscopic
examination to lie outside it. Furthermore, one-third of the cases that we
thought earlier in our work might represent intracardiae fragments were
found at operation to be cxtraeardiac.

Fig. 2. — Method of implantation of a foreign body in the heart of a dog.

Such confusion makes it very difficult to assess the risks to health and
life of intracardiae missiles. During the past year, however, these problems
arose, arid it was- necessary to establish a working policy. This policy’' was
formulated from information borrowed from the medical literature, from our
own hypothetical concepts, and from a limited amount of previous e.xperimental
work on animals.

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AMERICAX HEART JOURNAL

If ^vas I'olt that certain cardiac foreign bodies should be removed, for the
followim!: reasons: (IJ to prevent embolus of the foreign body or associated
tlirombns. (2) to reduce the danger of bacterial endocarditis, (3) to prevent
recurrent ])oricardial effusions, and (4) to diminish the incidence of myocardial
damage.

For these reasons it Avas decided to remove half of the missiles presumed
fo he in the heart that came under our observation. Applicability of these
factors Avas determined, in part, by the size and location of the foreign body
and by clinical manifestations. Clinical evidence supporting these tenets has
aeeiimulated during the year.

The first and most obvious indication for remoA'al is the prevention of
c 7 nhohis of the foreign body or of on associated tliro^nbns. SeA'eral instances
of this accident have been recorded in the literature and tAAm additional eases
may be briefly noted here.

I'ljr. 3. — Typical prnloc.Trcllti.s surrountliiiFT the Imphantccl foreign body.

One of our jiationts developed, shortly after injury, a hemiplegia coming
from Ji thrombus in the left auricle. The foreign body lay in the intcrauricular
septum and right auricle. It Avas remoA'cd from the right auricle.-’''

A second and particularly significant ca.se has recently been described by
Ijicutonant Colonel Xicliol.“ In this instance the missile Avas in the left ventricle.
Fmbolism causing hemiplegia occurred over Iavo avcoIis after injiuy.

The second tenet, that certain foreign bodies should be removed to reduce
the dnvger of harferiat nidocardilis, Avas based in part on e.xperimental Avork
with dugs.* Foreign bodies Avere placed in various locations in the heart, and
bactcrml i-ndocardit is developed sponlaneon.sly. Fig. 2 shoAvs the manimr of

A-' fj\jtju ;

iiDUIKS TNT

iiiiplaiitation and .the t\:pe of foreign bodj’- used. Figs. 3 and 4 illustrate
typical resultant liaeteria] valvulitis and septic embolic infarcts. It was feared
that foieign bodies niiglit behave in the same way in human hearts.

Fig’. I. — Typic.il .septic embolic inCarcts of experimental bacterial endocarditis.

Our clinical supjiort for Ibis indication is not complete. One patient ran
a course suggesting subacute bacterial endocarditis with spiking fever, tachy-
cardia, and an acute episode of right upper quadrant pain with jaundice. Re-
sponse to .surgical removal of the missile and its associated thrombus from the
right auricle was immediate and dramatic, with prompt recovery from an almost
moribund state. Furthermore, in baeteriologic studies of four intra-auricular
foreign bodies, jiatliogenie organism.s grew from three of these foreign bodies.
One of these lay in a small abscess in the center of a mural thrombus in the
right auricle. Similar studies in five right intraventricular fragments showed
growth of bacteria in only one instance; here also the foreign body lay in an
abscess within a mural thrombus in the chamber of the right ventricle. No
baeteriologic studies are available on the four other cases.

G

AMEinCAX HEART JOURNAL

It cannot be said that those infected niduses represent true bacterial endo-
carditis nor that they would liave produced it. Nevertheless, these findings
liave encouraged us to remove tlie missiles.

The third reason for the removal of missiles is to prevent recurrent peri-
cardial eifu.don.s. Tliis point has been stressed in the medical literature. We
have seen two sucli cases, but the symptoms were not severe enough nor were the
fragments of .sufficient size to justify intervention. Size and clinical manifesta-
tions will inevitably govern surgical removal of cardiac missiles. Fig 1 shows
those that we have removed. We have elected to leave more than we have
removed; the former were, of course, both small and silent.

KIk. 5. — ro'.toro.HiJtfi ioi ami latoial ioentK''noi;i-ams demonstrating the original position of

the fragment in the right ventricle.

Finally, cardiac missiles should be removed to dinmiish the incidence of
mpoca rdial da mape.

Damage of the right ventricular wall overlying the site of a migratory
missile has been noted in one instance. Thi.s case is presented in some detail,
for it i.s of special significance in .several re.sj)ects. In particular it demonstrates
clearly that a foreign body, simply lying in the chamber of the heart, can
produce <mnsiderablo damage of the overlying myocardium in three months.
This cas(' further indicates that ojici-ative removal per se need not cause si"-
Tuficanl myocardial injury.

TwH. K., a 29-year-old infantry sergeant was struck by a mortar shell
fnmment in the ri-ht lower jwsterior aspect of his chest on July 21, 1944,
mar .St. Lo. France. Fluoro.scopy and roentgenograms (Fig. .3) .showed a
in.-tallio foreign F.dy jniLsating with the heart, lying in the anterior portion

HARKEX AND ZOLI^ : FOKEIOX BODIES IX HEART ' 7

of tJie liglit ^Gllt^iclG, just to the left of the iiiidline. Aii olectroccirdiograin on
July 25 (Pig. 6} showed only inverted T waves in the right-sided preeordial
leads CPi, CP 2, and CP.-?. By August 8 the T wave in OP3 had, become upright,
so that the tracing appeared normal.

At operation on August 15, the missile was grasped through an incision
ill the right venli-icle, only to he pulled from the forceps hy the wriggling
mjmeardium and to he lost from sight and palpation, in the lilood stream. The
technical details of cardiotomy have been presented elsewhere.'’

Fig:. G.— Electrocardiograms before the drst cardiotomy. The figures in Uie upper left
corner of each segment indicate tlie leads (Roman numerals for the limb leads ana Arabic
numerals for the precordial leads CFi to CFc). The date of tracing appears m lower margin
of the section.

After operation, the foreign body was found by roentgenograms (Fig. 7) to
be in the right auricle'over the opening of the inferior vena cava. On August 17
the electrocardiogram (Fig. 8) showed elevated S-T segments in Leads I and II.
wiiicli fell by September 1. Later the T waves also became sharply inverted in
Leads I and II and in the left-sided precordial leads CF^, CP.r„ and CFc-
This pattern suggests acute anterior wall myocardial damage and may be
related to the incision made in the right ventricle near the septum in the
anterior surface of the heart, or to the associated pericarditis.

At a second cardiotomy on Nov. 16, 1944 (three months later), the missile
was visualized and palpated in the right auricle ,]ust above the entrance of the
inferior vena cava. It escaped again, however, and fell back into the right
ventricle to the position seen in the postoperative roentgenogi’am (Fig 9). A
significant point is demonstrated b.y tlie.se roentgenograms; that the imperfect
lateral position gives the impression that the missile is in the chest wall. Elec-
trocardiograms (Fig. 10) showed no specific acute change following this second

9

MAIv’KEN AXD 'AOLIjI

FOREIGN BODIES IN HEART

caidiotoiny, but only a progressive return toward normal of tlie T waves in
Leads T, IT. CFr„ and OF,;., ,

On Feb. 19; 1945, a tliird eardiotoniy was performed, again through an
anterior approach similar to the first operation. The old scar of the first incision
in the right ventricle was found to be solidly healed after this interval of six
months. Considerable fibrous pericarditis had developed but it did not limit
cardiac motion nor obstruct blood flow. Near the apex of the right ventricle.

ventricle after tlie .second 'unsuccessful eardiotoniy.

Fig. JO. — Electrocardiogram taken after the second cardiotomy.

however, the muscle wall ivas thin, flabby, and discolored ; the foreign body was
palpable in the .underlying right ventricular cavity. This area of myocardial
damage had been produeed by the muscle wall rubbing over the fragment dur-
ing the three months following the second operation. The heart was opened
again through this flabby area, and the shell fragment (Fig. 1) was grasped by
forceps and removed with only moderate difficulty (Plate I). The period of

0

10,

AMERICAN HEART JOURNAL

iiitriieardiac manipulation extended for approximately three minutes, in three
episodes. Showers of extrasystoles were noted during the process of removal.
The cardiac behavior at this time is recorded in the electrocardiograms (Fig. 11)
that are discussed later.

I’ is. II. — Electroc.'ircliographic tracings taken during the successful cardiotomy at the time of
removal of tlie fragment from the right ventricle.

11

HARKEN AND EOLL : FOREIGN BODIES IN HEART

Convalesceiice following operation was uneventful. Postoperative electro-
(*ai(liograin.s (Pig. 12) showed onty left axis deviation and low or inverted T
waves in Lead I and the preeordial leads, findings which were consistent Avith
pel icai dial reaction and residual minor damage in the mid-precordial area.

Pig. 13 recapitulates tJie migration of the missile from the right ventricle
to the right auricle and back again. Pig. 14 shows the patient clinically well
at the time of discharge.

Kip’. I.'!. — Difigrranimatic pi'csciiitation of the patient’s po.sition at operations and of tlie

migi'ation of the missile.

Ill the only case in tliis series of a foreign body in the left ventricle, the
missile lay in a small cystic myocardial hernia (Pig. 15). Roentgenkymographic
studies showed diminished amplitude of pulsation at the apex and passive left
ventricular dilatation during systole, suggesting early ventricular aneurysm or
hernia. Electrocardiograms (Fig. 16) showed a persistent pattern character-
istic of extensive damage of the anterior wall of the left ventricle. The ehanges
consi.sted of low voltage, deep Qi, absent Ri and inverted Ti, together with in-
verted and “W-sha]ied” QRS complexes and sharply invei-ted and coved T
waves in the left-sided precordial leads.

At operation, the foreign body was found in the left ventricle, in a cystic
zone of myocardial damage 1.5 cm. in diameter. It was ballottable in the
defect in the cardiac wall, and paradoxical pulsation of this area of the ventricle
was noted. The missile (Fig. 1) was removed without hemorrhage because of a
mural thrombus. The thrombus was not disturbed. The myocardial defect
was closed and reinforced with two .superimposed pericardial grafts. It is
interesting that electrocardiographic tracings taken frequently during the
operation showed no evidence of cardiac irritability at any time, except for a
few ventricular extrasystoles during the process of endotracheal intubation.

12

AMEniCAX HEAHT JOURNAL

Direct observation at operation indicated that the danger of rupture of
this myocardial hernia was real and was aggravated by the presence, of the
foreign body. It is thought that this operation in whicli the missile was removed
and the defect was repaired prevented progression of the myocardial damage
and possible ruptiu-e of the heart.

Fig. 14. — Patient LcR. R. at the time of discharge.

HAUKKN AND ZOLL : POUEIGN BODIES IN HEART

13

A third patient was seen by Major Fred Jarvis.® In this case, the wall
of the right’ ventricle overljnng a migratory missile degenerated and death
ensued.

A fourth ease, this from onr own series, seems particularly significant in
that it demonstrates in combination several of the tenents under discussion.

This soldier developed an empyema (hemolytic staphylococcus aureus and
Clostridium welchii) following injury by a shell fragment in the left anteiioi
aspect of the chest. The empyema was treated by decortication and, later, bj
open drainage before he arrived at the IGOtli General Hospital Che.st Center.
Three massive and two minor episodes of hemorrhage occurred in the six months
following injury; there were also bouts of jiyrexia reaching 103 F. that did not
appear to be due to the empyema. Fig. 17 shows the size and location of the
foreign bod}^ and Fig. 18 presents typical electrocardiographic tracings. Be-
fore operation there were right axis deviation Avith Ioav Hi and deep Si, low
diphasic Ti, and upright pointed To and T 3 . The preeordial leads Avere normal.
These findings did not help in localization of the mis.sile.

At operation on May 18, 1945, the empyema AAms found to communicate
with a laceration in the pericardium and underlying adherent left auricle.
There Avas a. laceration of the auricle that aa^s plugged by a large infected intra-
cardiac hematoma. The 2 by 1 by 1 cm. missile AA’^as wrapped in cloth and lay

AMT:niCAX IIKAUT .lOritXAL

1 1

in lliis {“lol. The Iragiaent was removed from the left auricle together with
the cloth and the infected clot. CL wdchii and Escherichia coU were grown
on direct culture of the foreign body. The surgical exposure, location of the
pericardial laceration, and type of repair arc described elsewhere.^

Kifr. n. — Poetcroanterior and lateral roentgenogram.s of a fragment in the left auricle. Radlo-

opaquo oil is seen In the empyema pocket.

KIk. IV. — r,l.-(qr..r)ird!i.i:ram« bffoic operation in the patient v\ilh loft auricular lacer.ition

and an Intra-auricular .>5hell fraKinent.

After operatum there was rajiid improvement of the empyema, and no
nulher episodes of hemorrhage or jtyrexia occurred. Electrocardiograms
I Fig. IP) sliow deep ami sharp inversion of Tj ami inverted T waves in CF.-,.
but no other .significant change. This case appeared to embrace mo.st of the
indications tor removal of an intraeardiac foreign body: extensive thrombus
with potential embolus. gros.s intraeardiac contamination and infection, peri-
‘•urdtul involvement, ami tlamagcd myoear.lium with repeated hemorrhage.

HARKEN AND ZOLE : FOREIGN BODIES IN HEART

15

Two additional factors may assume importance in the decision to remove
intracardiac foreign bodies : namely, pom and cardiac neurosis.

Pain has been associated Avith some of the pericardial missiles but Avith
only one of the intracardiac group. This Avas in a man in Avhom the missile
had migrated from tlie auricle to the ventricle. A similar case is described by
Lieutenant Colonel Miscall.'’

Cardiac neurosis may become an important consideration in spite of every
effort to reassure the patient. All our patients Avith foreign bodies in or near
their hearts have AA^anted them removed. Professor Grey Turner has said:
“In addition to the characteristic cardiac sjnnptoms just mentioned, there may
be neurotic manifestations Avhich mainly depend on the attitude of the patient
to the ImoAAdedge that he harbors a foreign body in one of the citadels of his
Avellbeing. ’

These are fragments of clinical evidence directing the surgeon to remoA^e
the larger or symptomatic missiles. The experience has been brief, yet con-
Auncing to us. It is emphasized that we decided to leave fifteen fragments
in the heart. These, of course, Avere small and silent. Surgery Avas underteken
in four additional cases Avhere intracardiac fragments Avere present. Two of these
fragments Avere deemed too hazardous to remove at exploratory pericardiotomy,
and tAvo Avere not recovered at cardiotomy.

h;

AMEKICAX HEART JOURNAL

I'Jie cost of operation to the patients has not been great; none died; all
have done ^Yell and apparently have normally functioning hearts now. Pinal
conclusions cannot be drawn for several years.

BEHAVIOR OF THE HEART DURING MANIPULATION

The teclinique used in approaching and removing cardiac and mediastinal
foreign bodies cannot be discussed here. During this experience, however, some
elementary rules of surgical conduct governing exposure and manipulation of
the heart have become clear. Some salient features of cardiac exposure are the
followng ;

1. Adequate direct exposure of the involved region. This requires the use
of a variety of approaches.

2. The conservation of the skeleton of the thoracic cage. Bone and carti-
lage may be divided but not removed. After operation there should be neither
deformity nor defect.

3. Minimal dislocation of heart from the position of optimal function.

4. Maintenance of moist cpicardium in the exposed heart. One per cent
novocaine solution has been used; it may have additional advantages in reduc-
ing cardiac irritability.

It is with the third principle of exposure that the remainder of this dis-
cussion is to deal; namely, maneuvers that are not tolerated well by the heart
during intracardiac and pericardial surgery. One case of an extracardiac and
one case of an intracardiac operation will bo used as illustrations.

The first demonstrates the effect of dislocation of the heart from the position
of optimal function during the removal of an extracardiac foreign body that
lay in a pericardial abscess well back on the diaphragmatic surface. The
location of the pericardial missile can be seen in the roentgenograms in Fig. 20.
At operation the foreign body was found on the posterior phrenic surface of
the heart in a pericardial abscess containing about 18 c.c. of pus. To gain access
to this area the heart had to be lifted out of the pericardial sac (Plate II).
Because tliis procedure caused fall in blood pressure and circulatory failure,
the heart had to be replaced frequently for rest and return of blood pressure
toward normal after relatively short periods of dislocation. IMany irregularities
in rhythm tliat were apparently extrasy. stoles occurred. Also, a marked cardiac
dilatation, particularly of the right ventricle, developed, Avith the result that the
heart became too large for the pericardial sac (Plate III).

Electrocardiographic tracings taken during operation (Fig. 21) showed varia-
tions in rhythm consisting of ventricular cxlrasy.stoles (at 300), wandering pace-
maker (varying P-R interval at 302 and 307), and A-V nodal rhythm (at 313,
3lo, and 310). It was at the time that the nodal rhythm occurred that a
l)articularly ]n-olongcd and alarming episode of eirculatoiy failure developed
•luring a period of dislocation of the heart ; after recovery, normal sinoauricular
tachycardia returned (at 317. 31?). and 332) (Pig. 21).

An additional change in the electrocardiogram Avas also related to disloca-
tion {»f the heart. At the S wave became broad and notched and the QBS

liAPvKEX AXD ZOLL: ForiEIGX BOMES
IX AXn IX }lELATIOX TO THOKACIC

Beood .Vessels axd Heart

Am. Heart J.
July. 1946

Plato II.

Plate I. — Colored photograph at thc
instant oC incision into the right venti’icle.
This is the third cardiotomy in Fig. 13.

Plate II. — Colored photograph illus-
trating the maneuver of dislocation of the
heart from the pericardial sac.

Plate III. — Colored photograph show-
ing marked right ventricular dilatation fol-
lowing dislocation of the heart. Plates II
and III were taken during the operation re-
corded in the electrocardiographic ti’acings
in Fig. 21.

Plate HI.

Plate I.

18

AMERICAN HEART JOURNAE

interval lengthened to 0.13 second, in contrast with the normal complexes which
were present at 207 and 237 before cardiac manipulation. It is unfortunate that
this abnormality was recorded in Lead II only, but it may be regarded as
indicating, at least, intraventricular block or luindle branch block, probably
of the 7’ight side. The abnormal QRS complexes persisted throughout the
operation, but the complexes had returned to normal four days later. This
delay in conduction was found, by direct visual inspection, to be correlated
with dilatation of the right ventricle, certainly an unusual observation in the
human subject. It may be considered, in part at least, a result of the increased
time necessary for the conduction of the impulse through the greatly dilated
right ventricle.

The intolerance of the heart to dislocation was demonstrated in this case
in two ways : first, by the ventricular dilatation, with incomplete bundle branch
block, and second, by varying types of arrhythmia and circulatory collapse.
Dislocation of the heart may produce torsion of the great vessels and obstruction
to outflow of blood, with fall in blood pressure resulting from the diminished
cardiac outputj and with ventricular dilatation from the increased resistance to
blood flow.

This type of experience has led us to avoid the apical suture as a means
of exposing inaccessible areas of the heart. Generally speaking, in elective
cardiac surgery, the approach can be so planned that precise and comfortable
exposure is provided for any part of the heart. The various techniques for
approaching different cardiac areas and chambers have received consideration
and illu-stration elsewhere.'^

Experience has also demonstrated that the classical hemostatic cardiac
grips, which are intended to provide a bloodless field, are badly tolerated. These
maneuvers upset cardiovascular dynamics and .should therefore be used only as
means of last resort.

The intolerance of the heart to obstructed blood flow is in sharp contrast
to its stability during other cardiac and intracardiae procedures. The surface of
the heart was manipulated, sutures were taken in the muscle, and actual in-
cisions were made into the chambers of the heart with little disturbance. It was
felt that keeping the surface of the heart moist with warm saline or novo-
caine solution Avas important in reducing the degi’ce of irritability. There Avere
minor evidences of irritability, such as extrasystoles, Avandering pacemaker
tvarying P-R inteiwal), and even A-Y nodal rhythm. Ususally these phenomena
Avere not accompanied by any significant clinical manifestations. Such minor
abnormalities Avere often produced by noncardiac procedures during anesthesia
and operation. They Averc often evoked by endotracheal intubation, spreading
of the riks, and manipulations of the hilar and mediastinal structures.

iilorc extensive manipulations inside the cardiac chambers by the exploring
finger or forceps to remove intracardiae thrombus or foreign lauly Avere less
well tolerated, though freriuently no abnormalities Avere noted. "Marked cardiac
irregularity in the form of multiple A-entricular cxtrasystoles Avas commonly
soon. The patient Avith the three cardiotomics, already discussed, demonstrated

HAEKEN AND ZOLL : FOREIGN BODIES IN HEART

19

this particularly well. Fig. 11 shows the electrocardiogram obtained as the
foreign body was grasped and extracted from the right ventricle. There were
showers of ventricular extrasystoles from varying foci in both ventricles, pro-
ducing runs of ventricular tachycardia up to sixteen seconds in duration. Direct
observation of the irregular heart action and examination of the electrocardio-
gram did raise the fear of impending ventricular fibrillation. At the end of
the procedure, however, upon the removal of the irritating forceps and missile
from the ventricular chamber, the ventricular tachycardia ceased promptly and
the P-R interval returned to normal in three beats. In our experience so far,
these irregularities have lieen relatively benign.

SUMMARY

Evidence is. presented in support of the following indications for the
removal of some intracardiac foreign bodies: (1) to prevent embolus of the
foreign body or associated thrombus, (2) to reduce the danger of bacterial
endocarditis, (3) to prevent recurrent pericardial effusions, and (4) to diminish
the incidence of myocardial damage. The additional factors of pain and
cardiac neurosis are also considered.

The behavior of the heart during various types of manipulation is
described. Dislocation of the heart from the position of optimal function is
poorly tolerated, as are other procedures whicli upset cardiovascular dynamics
by obstruction to blood flow.

REFERENCES

1. Aristotle: De Partibus Animaliuin, Lib. Ill, Cap. 4.

2. Paget, S.: The Surgery of the Chest, Bristol, 1896, John Wright & Co., p. 121.

3. Eelm, L.: Verhandl. d. Gesellsch. d. Naturforscher und Aerzte, 1896.

4. Decker, H. B.: Foreign Bodies in the Heart and Pericardium — Should They Be Eemoved?

J. Thoracic Surg. 9: 62-79, 1939.

5. Harken, Dwight E. : Foreign Bodies in and in Relation to the Thoracic Blood Vessels and

Heart. I. General Considerations and Technique of Removing Foreign Bodies From
the Cliambers of tlie Heart, Surg., Gjmec. & Obst. (To be published.)

6. Nichol, Arthur D. : Personal communication.

7. Harken, Dwight E.: Experiments in Intracardiac Surgery, I. Bacterial Endocarditis,

J. Thoracic Surg. 11: 656-670, 1942.

8. Jarvis,- Frederick: Personal communication by Paul C. Samson.

9. Miscall, Laurence: Personal communication.

10. Turner, G. Grey: Foreign Bodies in the Heart Twenty-three Tears, Surgery 9: 832-852,

1942.

11. Harken, Dwight E., and Williams, Aslibel 0. : Foreign Bodies in and in Relation to tlie

Thoracic Blood Vessels and Heart. II. Migratory Missiles, Am. J. Surg. (To be
published.)

EXPERIENCES WITH DICUIMAROL (3,3'i\rETI-IYrjENE-BIS-[4-
nYDEOXYCOUMARIN]) IN THE TREATMENT OP
CORONARY THROMBOSIS WITH IMYOCARDIAL
INFARCTION

Preli:mikary Report

Iratcxg S. Wright, M.D.

New York, N. Y.

F ollowing tlie discovery, isolation, and sjnithesis of dieninarol the anti-
eoagnlant properties of this and allied substances were demonstrated in
animals by Link and his co-workers^ and by Bingham, IMeyer, and Pohle.- Im-
mediately, several gToups of clinical investigators initiated studies to deter min e
the effectiveness of this substance in the prevention and treatment of thrombo-
phlebitis with and without puhnonary or other embolic phenomena.®'® The
technique for its use and the remarkable success achieved are now a matter of
established record.

Early in our studies at the Vascular Clinic of the New York Post-Graduate
i\redical School of Columbia University, we considered the possibility of the use
of this therapeutic agent in the treatment of coronaiy thrombosis. It is ex-
tremely difficult to evaluate its effectiveness in a particular patient avIio has
suffered from an uncomplicated attock of coronaiy thrombosis in its early stages
since we are, at present, unable to predict with certainly which patient will
have a rapid series of secondary' episodes of thrombosis, which one will have one
or more embolic phenomena, and ivhich patient will prove to have an uneventful
rccoveiy fi'om the immediate attack. It is recognized that the patient who ha.s
a series of episodes of thrombosis in different radicals of the coronary tree with-
in a short period of time or whose original thrombus propagate.?, extending
centrally and thus blocking off additional branches of the same coronary artery,
has an increasingly serious prognosis with each episode or extension. Experience
has clearly demonstrated that once a person has more than two episodes of
thrombosis within a period of three to four weeks there is a strong likelihood
that further episodes will follow and that the prognosis is poor. The author has
personally eared for many patients through such a coui’se, helpless to prevent
repeated attacks of thrombosis and death. In the same manner, once a patient
has developed a mural thrombus and has had one or more embolic phenomena,
the prognosis is grave indeed ; especially if the mui-al thrombus is in the right
heart thus producing pulmonary emboli.

fnlif G.-Ilifoinia Heart Associnlion. Stanford TJniv*>r.‘-ity. San Finnci‘.co,

Iti e.-ivp.'i tar evibllc.illon Jan. 21. isxc.

20

\'

WRIGHT: DICUJMAROL IN TREATMENT OP CORONiVRY THROJIBOSIS 2l

Tile first patients in this group to receive dicuinarol were selected because:

1. They had snfiercd rcjieatcd episodes of innltiple thromlii in different areas
of the coronary t.rce or the original thrombus had propagated. The clinical
evidence for these criteria consisted of repeated attacks characteristic of the
coronary syndrome vdth precordial pain, fever, leiicocytosis, and increased
sedimentation rate, with confirmatory electrocardiographic findings.

2. They had suffered repeated embolic phenomena either pulmonary or to
other ai’eas. (It was recognized that certain of the pulmonary emboli might
have arisen in the extra cardiac circulation, but following myocardial infarctions
tlie percentage of pulmonary emboli is a considerable one and, from whatever
source, repeated pulmonaiy emboli have an increasinglj’- serious prognosis.)

3. They had evidence suggesting that both Factor 1 and Factor 2 were
active.

TJnfortunatelj’’, previous^ compiled adequate statistical data regarding the
prognosis of each of these special categories in patients not treated by anti-
coagulants are unavailable. This fact combined with the difficulty of running a
properly controlled series for each of the suitable subdivisions has mitigated
against the drawing of final conclusions regarding the value of dicumarol in
the treatment of coi-onary thrombosis.

The first patient in this series was treated with dicumarol in May, 1942.
Since then, 76 patients with acute or recurrent coronary thrombosis have been
treated with dicumarol by the author or under his direction.' These have been
in both civilian and Army hospitals. Forty-three of these were selected because
they qualified under one of the aforementioned categories as having a serious
prognosis. Twenty-eight had evidence of multiple thrombi or propagation, 12
had multiple embolic phenomena, and three showed evidence of both tjTpes ol
episodes.

The experience with these groups encouraged us to increase the series by
using this substance in 33 patients suffering from uncomplicated first or second
attacks of coronary thrombosis.

In addition to dicumarol, aU patients received conventional treatment in-
cluding rest, opiates, barbiturates, aminophylline, and oxygen according to the
indications.

A total of 15 patients died : 11 from the series of 43 with the more serious
prognosis and four from the series of uncomplicated cases. Only four of the
deaths occurred as a direct immediate result of the insult of the thrombosis.
Three of these were in the complicated group and only one was in the uncom-
plicated group. Eleven deaths occurred as a result of cardiac failure two or
more , weeks after their last acute episode. Of these, eight were in the com-
plicated group and three were in the uncomplicated group. Eight autopsies were
performed. No evidence of hemorrhage or any other effects of dicumarol, which
could have produced death, were found. The livers from three patients shovmd
slight fatty infiltration which was not considered to be of serious degree. Of the

22

AMERICAN HEART JOURNAL

43 patients in the complicated group, 38 ceased having evidence of extension,
additional thrombi, or embolic phenomena after the dicumarol therapy was in-
augurated.

Sixty-one patients recovered from the attack durmg which this study was
carried out. "While the over-all mortality figures do not differ markedlj^ from
the anticipated rate for single attacks of coronary thrombosis, certain facts
should be considered in tliis regard.

1. Forty-three of these patients were selected because they had complica-
tions knovm to be associated -with a veiy high mortality. (As mentioned
previously, exact figures are not available but 60 to 70 per cent mortality would
approximate the anticipated risk of this group of patients in the experience of
the author.) Only 11 (25 per cent) of these patients died in the episode for
which they were treated.

2. Of the 33 patients having their fii’st or second uncomplicated attack at
the time of onset of treatment vdtli dicumai'ol, four died (12 per cent) against
an anticipated death rate of 20 to 30 per cent.

The observation of individual cases seemed more suggestive. Abstracts of
several ease histoiles of particular interest are therefore included.

CASE HISTORIES

Case 39. — 50-year-old man was admitted to the hospital complaining of severe pre-
cordial pain of four hours’ duration which radiated down the left arm. He had suffered
from one previous recognized attack of coronary thrombosis nine months before. The first
attack had been diagnosed on the basis of precordial pain with prostration, fever, increased
sedimentation rate, leucocjdosis, and electrocardiographic tracings tju’cal of an anterior
myocardial infarction. Tlio patient was hospitalized for ten weeks and made an uneventful
recovery; he had only the single moderately severe episode. He was able to return to
administrative work and, aside from easy fatigability, Iiad no marked untoward effects.

Tlie second attack, during which the patient was hospitalized, was accompanied by
more severe pain and breathlessness. The second day the oral temperature reached 101° F.
Tlie .sedimentation rate rose until on the seventh day it reached 62 mm. per hour. Tlie white
count increased to 12,400 with 78 per cent polymorphonuclear cells. The electrocardiogram
which was normal on admission showed changes on the tliird day typical of an acute anterior
infarction as follows: there was a convex S-T segment with late inversion of the T waves
in Load 1, a concave S-T segment in Lead III, and an absent Q wave with an upright T wave
in I^ead IV. Serial tracings showed changes which tended to revert toward normal by the
tenth day. On treatment with rest, morphine, and whiskey he did well. By the twelfth day
the patient was comfortable, the fever had subsided, and the .sedimentation rate was down to
2S mm. per hour. He appeared to be on the way' toward an uneventful recovery when suddenly
ho was seized with an agonizing prccordial pain and once more developed fever wliich reached
103° F, This time the course was muck more stormy. He required oxygen therapy for his
dyspnea and cy.nno.ois, his liver edge extended down 2 fingerbreadths below the costal margin
and was tender, and the sedimentation rate increased to 70 mm. per hour. The white cell count
rO‘-e to 16,000 with 80 per cent polymorphonuclear cells. The electrocardiogram .shou'cd marked
changes again, but this time they were typical of a posterior myocardial infarction n-ith
some residual changes from the anterior infarction as follows: T, was isoelectric and there
wa.H a concave S T interval with a high origin in Lead IT, a deep T,, and absence of R, with
deep T,. The rhythm was regular.

Wright : DicuMAROL in treatment op coronary throsebosis 28

A third episode occurred seven days later and his precordial distress became more con-
stant. He was dyspneic and cyanotic and was kept in an oxygen tent constantly. The
electrocardiogram .showed further disturbance suggestive of posterior wall damage.

DJcumarol was started immediately after the third attack in the hope of decreasing the
tendency toward further thromboses. It was administered .according to the technique out-
lined later in this paper. The prothrombin time was kept as closely as possible between 30 and
35 seconds for thirty days. The patient’s course was uncertain for one month but he gradually
improved and after three and one-half months he was having only moderate discomfort and was
able to leave the hospital. There were no evidences of the formation of additional thromboses
nor of propagation of former thromboses after the inauguration of dicumarol therapy.

As noted earlier in this report no one can say with certainty whether or not
dicumarol influenced the course of this patient by tipping the balance away
from a tendency toward thromliosis. Nevertheless, this type of historj'^ was
repeated sufficiently often in this series to warrant giving serious consideration
to the possibility of such an action.

Case 42. — A 36-year-old man was admitted to a hospital complaining of precordial pain
of moderate .severity and mtliout radiation. He had suffered from the anginal sjmdrome
produced by effort for two mouths prior to the present acute episode. He had an oral tem-
perature of 100° F. on admission. The second day this rose to 101.5° P. and then slowly sub-
sided. On rest with morphine, the pain disappeared within thirty hours. The sedimentation
rate reached a peak of 30 mm, per hour on the fifth day and the white count reached 11,400
with 76 per cent polymorphonuclear cells. The electrocardiogram .showed typical changes of
a posterior (T, type) myocardial infarction on the second day with a tendency toward rever-
sion to normal b}' the seventh day. His course was mild. By the sixth day he felt so well
that it was difficult to keep him in bed. On the ninth day he had a sudden sharp pain in the
right posterior chest associated with some difficulty in breathing comfortably. The next day
ho coughed up bright red stained sputum. A pleural friction rub was readily heard over the
right lung base posteriorly on normal breathing. No evidence of peripheral thromboplilebitis
could be found on physical examination. X-ray films showed a shadow characteri.stic of a
small pulmonary infarction in the right lower lobe laterally.

Four days later there was a recurrence of acute pain in the right lung base posteriorly
and again bright red blood was raised by cougliing. Two days after the second episode
a third one occurred, this time in the left limg base.

It was believed that the patient had developed a mural thrombus in the right heart,
following his myocardial infarction, from which segments of fresh thrombus were breaking
off to become pulmonary emboli. The possibility of an undetectable thrombus existing in an
extra cardiac vein was also considered as a source of the pulmonary emboli.

Kegardless of which source was correct, anticoagulant therapy appeared logical and
dicumarol was given according to the technique set forth elsewhere in this paper. It was
continued for one month.

During the first two weeks a prothrombin time of approximately 30 to 35 seconds was
maintained. During the second two weeks this was gradually allowed to revert toward normal.
No further pulmonary emboli occurred after the dicumarol therapy was started.

While it is recognized that minute pulmonary emboli may occur which
cannot be diagnosed during life, we can safely state that none of clinical
significance occurred following the use of dicumarol. Again 'we cannot prove
beyond a doubt that dicumarol affected the course of this syndrome, hut the
possibility is certainly worthy of consideration.

Case 18. — ^A 47-yeaf-old man was admitted to the hospital Nov. 26, 1942, complaining
of increasing dyspnea on exertoin. He gave a history of hypertension which was first recog-

24

AiMERICAK HEART JOURNAL

nized in 1934. Between 1934 and 1942 the systolic blood pressure had varied between ICO and
200 mm. of mercuiy. He did not know the diastolic pressures. The patient had no symp-
toms. One brother and two sisters had hypertension. In August, 1942, the patient observed
that he became dyspneie after walking only three blocks. Tliis was fairly constant. One
evening (exact date uncertain) in September, 1942, about 8:00 P.Ji., Avhile lying in bed,
he suddenly became very dyspneie. He began to wheeze and at the same time developed pain "
in the lower substernal area which radiated to the shoulder. This attack lasted fifteen minutes
and then completely disappeared without medication. A blood pressure reading taken shortly
afterward showed the usual elevation. There was no history of previous attacks of breathless-
ness or of any form of allergy.

On physical examination on admission, the patient did not appear ill. The blood
pressure averaged 200/150. He had an emphysematous tj’pe chest that was hyperesonant to
percussion. There were no rales in the chest. The fundi showed copper-wire arteries. All
peripheral pulses 'were strong. The heart was enlarged to the left and downward. The apex
lx;at was felt just lateral to the mid-clavicular line in the sixth intercostal space. At times
a triple thrust was felt in the apex region. There was a booming first sound at the apex and
an accentuated aortic second sound. No murmurs could be heard. There was occasionally
a gallop rhjihm at the apex accompanied bj' pulsus altemans. No friction rub was heard.

Blood counts, serology, and urine analj'sis were normal. The highest sedimentation rate
was 30 mm. per hour. X-ray films of the chest indicated left ventricular enlargement and some
pulmonary congestion. The first electrocardiogi-am revealed left ventricular preponderance
and evidence of myocardial damage compatible with a previous anterior myocardial' infarction
(T, type).

The day after admission the patient became dyspneie. The liver was enlarged to about
4 cm. below the costal margin. The neck veins became engorged and moist rales were heard
in the chest. Mercupurin was given; diuresis ensued, the rales disappeared, and the liver be-
came smaller. It was necessary to give mercupurin about every five day’s in order to keep
the urine output approximately equal to the intake. On the fourteenth day after admis.sion
the patient developed epigastric pain, wheezing, and went into mild collapse. The pulse became
rapid and thready and the blood pressure dropped to 140/90. A low-grade fever was noted.
Electrocardiographic studies showed evidence of a superimposed anterior infarct (T, type
with coving). A pericardial rub developed at the apex. At this time a left ventricular
aneurysm was suspected on the ba.^is of x-ray' findings. Because of the prognosis and Ihc
po.'ssibility of propagjition of the original thrombu.s, the development of new thrombi, and flie
development or extension of mural thrombi we decided to use dicumarol. It was administered
according to a somewhat lower schedule of dosage than outlined elsewhere in this paper, tlie
prothrombin time being kept between 26 and 30 seconds. A total of 1,500 mg. of dicumarol
was given. No evidences of hemorrhage were ever noted.

On the twenty-first day the patient went into mild peripheral failure and pulmonary
edema. Digitalis was then cautiously administered. On the thirty-first day ventricular extra-
systoles developed. Quinidine was given to prevent ventricular fibrillation. On the thirty-
second ho.spital day' the patient slumped forward in bed and died suddenly'.

The .significant autopsy findings were as follows: The pleural, pericardial, and peri-
toneal cavities were free from c.xcessive fluid. The lungs were slightly' heavy' and more
reddish brown than usual. No infarctions were noted. On section the. alveolar walls were
thickened in some areas and ruptured in others. The heart weighed .570 grams. It })rescnled
the configuration of the essential hy'pertensivc heart with hypertrophy of the left ventricle.
,Vt tlic sipex lliere was a small aneurysm of the left ventricle whicli measured 3,5 cm. in
diameter. It projected <iut about 1..5 cm. beyond the surrounding heart tissue. Tlie left
coronary rulcry- was tortuous and contained numerous cah-itic j)laques. .Tust beyond the
origin of ihe left coroiuiry artery the lumen was oblit«*raicd by ilense, gniyish-white tissue
apparently repri'scnting an old organired thrombus. The sirea of occlusion measured J.8 cm.
in length. I’ive cenfimeter.-i beyond the disfji! extremity of this thrombus another occlusion was

WRIGHT: DICUJMAROL IN TREATMENT OP CORONARY THROMBOSIS 25

present. It measured 0.5 cm. in length and consisted of reddish-gray, somewhat stratified,
tissue. Tiro right coronary artery showed only slight atherosclerosis. Section through the
heart re\ealed the middle part of the major portion of the left ventricular myocardium to
consist of yellowisli, necrotic, fattylike tissue. The area of necrosis measured 4 to 7 mm. in
\ridth. The subepicardial and subendocardial myocardium adjacent to the infarct appeared
grossly normal. The wall of the aneurysm measures 3 mm. in thickness. Two of the
intertrabecular recesses of the aneurysmal portion of tlie left ventricle contained dry, granular,
reddish-gray masses representing a small mural thrombus. The outer surface of this mural
thrombus appeared to be well sealed off by fibrin. The myocardium of the interventricular
septum showed extensive areas of scarring. The left ventricular myocardium measured 14
mm. in thickness. The right ventricular myocardium measured 3.5 millimeters. The valves
were competent and of tissue paper thiclmess, and the circumferential measurements were
w'ithin normal limits. Histologic sections showed all gradations between frank necrosis and
early degenerative changes in the left ventricular myocardium. A section of the mural
thrombus indicated that it was relatively recent consisting of irregular anastomosing homo-
geneous acidophilic laminae with tlie spaces between containing fibrin, red blood cells, and
leucocytes. Five sections of the left coronary artery were studied. In all five sections, the
intima was markedly thickened by a connective tissue matrix containing calcific deposits, clefts
having the configuration of cholesterol ester crystals, and scattered lymphocytes. In several
other sections the lumen was eitlier completelj’ obliterated or reduced to small slitlike apertures.
In one section the lumen was occupied by an organized thrombus and was partially re-
canalized. In other sections the vessel contained a relatively recent ante-mortem thrombus.

The determination of the effect of dicumarol in this case is difficult, if indeed
aiij' can lie demonstrated. The dosage was small and the prothrombin time was
kept lower than was the case with later patients. This case does illustrate
clearly tlie complicated picture which is not infrequently encountered. We
found evidence of one large and multiple small occlusions, at least some of which
may well have occurred at the time of the acute episode of September, 1942. A
major recent occlusion was found in the more distal portion of the left coronary
artery. This probalily occurred with the acute episode of Nov. 12 to 13, 1942.
There was evidence of acute myocardial infarction, a ventricular aneuiysm, and,
of particular interest in this instance, a small mural thromlius in the aneurysm.
If this thrombus increased in size, it was perfectly capable of liberating emboli.
It was, however, sealed over and no embolic phenomena were discovered.
Whether dicumarol played a part in preventing emboli in this case we cannot
say. Its use would seem indicated. As in Case 21 dicumarol could have no
effect on the course of the condition once the myocardium was sufficiently
severely damaged.-

Case 21. — ^A 42-year-old man was admitted to the hospital complaining of ''tearing”
substemal pain which radiated into the neck. He developed a fever of 103° P. on the second
day. His sedimentation rate rose to 46 mm. per hour and the highest white count (fourth
day) was 12,400 with 77 per cent polymorphonuclear cells. The electrocardiogram showed
the pattern of anterior myocardial infarction (T, type). On routine treatment he improved
for six days. Suddenly, while eating, he was seized with a severe pain in the right lateral
chest which persisted for two days. The second day he coughed up bright red blood. 'Ho fric-
tion rub could be heard, but an x-ray film showed a .shadow compatible with a pulmonary
infarction in tlie right lower lung field. His heart then developed auricular fibrillation and be-
gan to show evidence of decompensation. The following day he had a second similar pulmonary
episode in the left base and two days later one in the right middle lung field.

26

A5IERICAN HEART JOURNAL

Dicumarol was started on the ninth day and administered according to the technique
outlined in this paper. No further recognizable embolic phenomena occurred after dicumarol
therapy was instituted. The patient, however, pursued a progressively downhill course and
became more severely decompensated. He became orthopneic, moist rales were heard finst
over both lower lobes, later throughout both lungs. His liver became enlarged and tender,
and dependent edema appeared. Oxygen therapy, aminoplu'lline, mercurial diuretics, and
digitalis were used without favorably affecting the course of the patient.

Ho expired thirty days after the onset of his attack and twenty-one days after dicumarol
therapy was instituted. The prothrombin time had fluctuated rather widely during the disturb-
ance in fluid equilibrium occasioned by the decompensation, ranging from 23 to 52 seconds, but
at no time was there e^ddence of any hemorrhagic manifestations other than a small purpuric
spot on the left thigh and some minor hemorrhagic areas at the sites of venipuncture in both
arms. These were such as might be seen in the absence of dicumarol therap 3 ".

Autopsj' revealed the following significant findings: The lungs showed tj'pical signs of
congestive heart failure. In addition there were evidences of one large, old infarct in each
lower lobe and of numerous scattered Small infarcts. It was believed after examination that
probably none had occurred within a period of two weeks before death. The liver weighed
1,345 grams and showed some evidence of passive congestion with cloudj' swelling. The heart
weighed 530 grams. Both coronary arteries w’ere tortuous and contained numerous calcific
plaques. Five centimeters from the origin of the right coronar,v arterj- the lumen was
obliterated by a thrombus which was reddish-graj' and stratified. It extended about 2 cm.
and blocked off several branches of the arterj'. Sections from this area showed the myocardium
of the right ventricle to consist of necrotic, j'ellowish, fattjdike tissue. Microscopic studies
showed tj’pical findings of a recent massive mj’ocardial infarction. Attached to the endo-
cardial lining of the right ventricle was an olive-shaped, shinj’, mural thrombus 1.5 b)’ 3 cm.
in size. On section it appeared to be relativel}' recent in origin but was completelj' sealed off
by a laj'or of material resembling fibrin. Other evidence of possible sources of the pulmonarj*
emboli, either intra- or extracardiac, could not be fotmd. Several old occlusions of minute
branches of the left coronaiy arterj' were found.

While we cannot with certainty that dicumarol prevented the further
propagation of the mural thrombus Muth a resulting cessation of pulmonary
emboli, the following points are in favor of this possibility :

1. The episodes of pulmonary embolism ceased following the inauguration
of dicumarol therapy. This was confirmed clinically and pathologically.

2. The mxiral thrombus, while recent in origin, was sealed off to a remax’k-
able degree.

3. No other sources of pulmonary emboli were found. (The po.s.sibility of
emboli coming from some obscure venous .source was not completely ruled out.)

On the other hand, as anticipated, the use of dicumarol did not affect the
course of the process once a massive infarct had occurred. The patient progressed
into a condition of cardiac insufficicney and death.

DISCUSSION

It has been olxseiwed by numerous workers, and confirmed by the author,
that when a thrombosis occurs either in a vein or an artery in one portion of
the body it is common, either simultaneously or within a short time, for multiple
thrombi to fonn in other pails of the vascular tree as well as for local propaga-
tion of the primary thrombus to take place. The exact mechanism which causes

WKIGHT; DICUMAROL IN TREATMENT OF CORONARY THROMBOSiS 27

this plienomenon has never lieen adequately explained. Perhaps the explanation
is the simple one of decrease in the rate of blood flow which occurs secondaiy to
placing the patient at complete bed rest, the most common procedure. Evidence
against this hypothesis is found in the work of Baumgarten,® Dietrich,'’ and
othei-s who have demonstrated that blood does not coagulate in a vein that has
been ligated carefully at both ends. We have found the clotting time and
prothrombin levels to be within normal limits in patients whom we have cheeked
during such episodes.^"

The question of the relation of the platelets to this occurrence is worthy
of comment. Hueck’*’ and von SeemeiP^ have reported a decrease in platelets
during the firat three to five postoperative days followed by a marked increase
in number. Similar observations have been made in tlie presence of inflamma-
tioiiin 12 malignant growths.'"’’ The agglutination tendency of the

platelets is considered to be increased when the globulin fraction and the
fibrinogen increase and the albumin fraction diminishes; in other words, when
a shift occurs toward coarse dispersion in the relation between the protein com-
ponents of the blood."'"’ Such shifts tend to take place after operations and
accidental trauma and in the presence of infections and malignant growths.

Starlinger and Sametnik’'’ have reported tliat as tlie shift toward the more
coarsel}^ dispersed globulins occurs the normal electrical cliarge of the platelets,
which is negative and hence repellent to the similarly negative proteins,
diminishes. This decreases the tendency to repulsion and hence increases the
tendency to agglutination.

Stuber and Lang'’^ have proposed an explanation for the diminished elec-
trical charge of the platelets. Their explanation is that a retarded circulation
results in increasing the carbon dioxide in the blood. This increases glycolysis,
which entails a decrease in the negative electrical charge of the thrombocytes
with an accompanying increased tendency to agglutination of the thrombocytes.

The action of thrombokinase released from cells as a result of surgerjq
inflammation, or malignancy might weigh the balance in favor of coagulation
and is worthy of further careful .study. Numerous other factors have been
discussed in this regard. For a review of this subject the reader is referred
to the comprehensive monograph by BiTizelius.’"

Multiple thrombosis is an extremely common occurrence in patients with
thrombophlebitis; it probably occurs in the majority of patients. Here again
available figures are of little significance since autopsy findings have revealed
that many thrombi may be present in various venous segments without being
detected, or indeed detectable, clinically.

That a similar phenomenon occurs in a definite group of patients with
coronary thrombosis is clearly demonstrated by following the clinical and electro-
cardiographic findings. This occurs in the absence of surgery or other trauma,
malignancy, and, in the strict sense, inflammation (at least without the basis
of infection). These patients characteristically have a typical primary episode

♦Recent unpublished work of Meyers and Poindexter suggests that minute increases in
the prothrombin level of the blood may occur as.sociated with coronary thrombosis.

28

AMERICAX HEART JOURNAL

followed at intervals of from seven to twent.y-eight days or more by reciUTeiil
atlaeks of pain, fever, leueoej'tosis, and increased sedimentation rate, with
elect I'oeardiogTaphie evidences of more marked involvement in the same area or
multiple involvement in other areas of the heart.

Autopsy findings showing multiple undiagnosed occlusions of the coronary
arteries also demonstrate that this phenomenon may occur without clinictil
recognition. Frequently a careful review of the history will reveal suggestive
symptomatology -whieli was not intei’preted correctly by the patient or his doctor.

Do these multiple episodes of thrombosis occur because there exists a pro-
found change in the thrombosing balance of the blood which is responsible for
l,he first and the subsequent thrombi wherever the vascular walls are conducive
to lids process? Is the change primarily a local one which initiates a generalized
change in the thrombosing balance of the blood ? Or is it primarily a widespread
vascular change ■which produces a condition conducive to thrombosis in numerous
focal points at approximatelj^ the same time? We cannot answer these questions
for either thrombophlebitis or coronary thrombosis at this time.

It is logical, from a physiologic viewpoint and on the basis of clinical
experience in the treatment and prevention of venous thrombosis and pulmonary
embolism, to utilize anticoagulant therapj* for the treatment of coronary
thrombosis where there is evidence of a tendency to additional thrombosis either
local, scattered in the coronary^ tree, or mural. It should be pointed out that
with the development of mural thrombi, thrombosis of the thebesian veins may
occur as a result of obstruction of their ostia. Cases have been observed where
the thrombi in the thebesian veins propag-ated into the larger venous sinuses.
Tills sequence of events tends to further damage the myocardium by interference
with its nutrition.’® This phenomenon is not as yet very widely recognized.

Dicumai'ol is the present drug of choice for this anticoagulant therapy.
If the situation is very acute, heparin may be used for the first twenty-four to
forty-eight hours until the action of dicumarol is established.

METHOD OF ADMINISTERING DICU:MAR0L

In our series the following techniques for administration liave been used :

1. The prothrombin time is determined (Quick or Link-Shapiro undiluted
technique^) before the first dose is given. The normal reading should be 1:1
to 17 seconds.

2. If tlie prothrombin time is normal or lower, 300 mg. of dicumai'ol
are administered orally in one dose.

3. Each morning the prothrombin lime is determined and reported to the
physician in charge of the case before the dicumarol dosage for that day is
determined.

4. Dicumarol is administered in 300 mg. doses daily until the prothrombin
time is 30 seconds, and in 100 or 200 mg. doses when the prothrombin time is
betwee n 30 and 35 seconds on the upward portion of the curve.

*Tho thromUdpl
Th«' tice of Ihrombopl
Cicum.-irol (lobaRC.

a-. tin tiBofl rnimt !)•• fro.sli and cliocKod aKain-^t a control for each tcfit.
aslln KivinK hlph control ngmes may prove dangerous In ini-sguiding the

WHrGHT : DICU^MAROL I2T TREATMENT OP CORONARY THROMBOSIS 29

5. AVlicn tlie protlirombiii time reaches 35 seconds diciimarol is discon-
iiinicd until it drops to below 30 seconds, when the drug may be given cautiously
in 100 to 200 mg. doses again.

6. Daily prothrombin times are determined. Frequently the time ma}"^ rise
for several days after discontinuing diciimarol but will then return toward
nonnal. It it reaches 60 or more seconds, hemorrhagic manifestations may
occur. In this series, the.se ivere confined to minor purpuric S] 3 ots in three
patients.

7. If more severe hemorrhagic manifestations should occur, they may be
checked by one or two whole fresh blood (may be citrated) transfusions of 300
to 500 c.e. each, by the admini.stration of vitamin K (Menadione bisulfite. 64
mg., in from one to four doses has proved satisfactoiy) , or both.

8. Diciimarol has been continued in most of these patients for thirty days
<after the last cpi.sode of thrombosis or embolism. The ob.ieetive has been to keep
the prothrombin time between 30 and 50 seconds especially during the first two
to three weeks. The dosage is then tapered off slowly pennitting the time 1o
drop to 25 to 30 seconds followed by a gradual return to normal.

.SUIUMABY AND CONCLUSIONS

It would be premature to make extensive claims about the merits of
diciimarol in the treatment of coronary thrombosis. Adequate controls with .
which to detemiine its value statistically are not yet available and will be of
little value unless several subdivisions depending on the severity, extension, and
complications of each group are studied separately. Each of these subdivisions
must contain a statistically significant number of controls and treated patients.
This will be a long and difficult but important evaluation.'' It did not seem
.iustified to await the final results of .such a study before reporting on the ex-
periences contained in this paper. We can conclude the following from these
experiences.

1. In no ca.se was there eridence that dieumarol aggravated or complicated
the course of a patient Ynth coronaiy thrombosis. The possibility that intimal
hemorrhage^”’ ”” might be a complicating factor was considered, but no evidence
was obtained in this serie.s, either clinically or pathologically, that this was of
significance in any case.

2. ■ On the basis of previous animal and human experience with dieumarol, it
appears physiologicallj’’ sound to use it ivhenever there is a definite tendenc.v
for a thrombus to propagate or multiple thrombi or embolic phenomena to occur.
Gcrtain cases of coronary thrombosis demonstrate definite tendencies in this
direction.

3. In numerous individual cases it has appeared that these thrombosing
and embolic tendencies have been interrupted by the use of dieumarol. Con-
sidering the degree of pathologic narrowing of the coronaiy arteries found in
.some heaihs, it is not .surpiising that occlu.sions did continue to occur in .some
patients on dieumarol therapy.

*Siich a .study i.s beiriK planned as a cooperative venture in ten hospitals under the
auspices of tlie American Heart Association.

30

AMERICAN HEART JOURNAL

4 . The mortality rates for tlie complicated and the uncomplicated cases of
coronary thrombosis treated with diciimarol appear to be lower than anticipated
for each group, but it is considered inadvisable to draw conclusions regarding
its effect on the moi’tality rate on the basis of so small a series and without care-
ful controls. Another factor which may have influenced these figures favorably
is the fact that the average age was jmunger than that usually considered average
for patients with coronary thrombosis. Fifteen were under 35 years of age;
only ten were above 60. hlueli more studj^- is esential to detemine this point.

5. In no instance was it felt that dieumarol influenced the rhythm or the
rate of the heart directly.

This study suggests that dieumarol may be of value as a preventive measure
against propagation, multiple serial attacks of coronaiy thrombosis within
short spaces of time, mural and thebesian vein thrombosis, and embolic
phenomena folloA\dng coronary thrombosis. A study of the use of dieumarol in
the treatment of such complications Avhen associated wdth auricular fibrillation
also seems justified. The value of the routine use of dieumarol in all cases of
coronaiy thrombosis has been considered. The material available to date does
not, however, justify the conclusion that dieumarol will affect the results in
uncomplicated cases of coronaiy thrombosis.'' It is also impossible to state to
Avhat degree it will affect the longevity of a patient Adth marked progressive
arteriosclerosis of his coronary arteries. Further investigation Avith large groups
of .such patients aauII be necessary to determine the ansAver to these questions.

There is no eAudenee that once dieumarol has been discontinued and the
blood prothrombin leA'el has returned to nonnal any effect is exerted AA'hich de-
creases the risk of further attacks of coronary thrombosis in the same individual.
Its continued use Jis a prcA'entiA'e measiu-e may be a subject for future studies,
but the risk of the use of this substance AAuthout careful frequent observation
of the prothrombin Ica'cI in the blood must be borne in mind.

REFERENCES

1. n. Campbell, H. A., Roberts, W. L., Smith, W. K., and Link, K. P.: Shidie.s of Hemor-

rhagic Sweet Clover Dl.^ease. I. The Preparation of Hemorrhagic Concentrates, J.
Biol. Cliem, 136: 47, 1940.

b. Campbell, H. A., Smith, W. K., Eoberhs, W. L., and Link, K. P.: Studies of Hemor-

rhagic Sweet Clover Disease. IL Tlic Bioassay of Hemorrhagic Concentrates by Fol-
lowing tlio Prothrombin in the Plasma of Rabbit Blood, J. Biol. Cliem. 138: 1, 1941.

c. Huebner, C. F., and Link, K. P.: Studies of Hemorriiagic Sweet Clover Disease. VI,

Tho Synthesis of the Delta — ^Diketonc Derived From the Hemorrhagic Agent Through
Alkaline Degradation, J. Biol. Chem. 138: 529, 1941.

d. Link, 1C. P.: The Anticoagulant Dieumarol, Harvey Lect. 34: 1(!2, IPl.T-ll.

2. Bingham, J. B.. Meyer, 0. O., and Pohle, F. J.: Studies of the Hemorrhagic Agent,

3_,3'.methylene-bfs-(4-h}-droxycoumarin) : Its Effect on the Prothrombin and Coagula-
tion Time of tho Blood of Dogs and Humans, Am. .1. M. Sc. 202: 59.3, 1941.

3. Butt, n, R., .Allen, E. V., and Bollman, ,T. L.: A Preparation From Spoiled Sweet

Clover, 3.3'-methylcne-bis-f4-hvdroxvcoumnrin) AA'hich Prolongs Coagulation and
Prothrombin Time of the Blood, Proc. Staff Meet.. Mavo Clin. 16: .3.38. 1941.

Abi.'t paner Im*! been i)rep.are(l, two favorable rct>ort.s bavo appe.ared, each ba.'-ed
'u mty CQ^i‘P nf coronary tbronibo'^is treated with dieumarol. .as follow.s: Nichol, E. S., and
E'cuiuarot Tliernpy in .Vcsite Coronary Thrombosis, .T. Florida M. A. 33: 3G.A.
ThromlnXl .\;73o;''3-ps-!^ Bramhcl, C. E.: Dieumarol in Acute Coronary

rayo,

194C

WRIGHT ; DICUMAROL IN TREATMENT OP CORONARY THROMBOSIS

31

4. a. Prandonij A., and Wright, I. S.: The Anti-Coagulants Heparin and the Dicoumarin-

3,3'-inethylcne-bis-(4-hydroxycoumarin), Bull. New York Acad. Med. 18: 433, 1942.
b. Wright, I. S., and Prandoni, A.: Dicoumarin-3,3'-methylene-bis-(4-hydroxycoumarin) ;
Its Pharmacological and Therapeutic Action in Man, J. A. M. A. 120: ‘1015, 1942.

5. a. Lehmann, J.: Hj’poprothrombinaemia Produced bj^ Methylene-bis-(hydroxj’’COu-

marin) i Its Use in Thrombosis, Lancet 1: 318, 1942.
b. Idem: Hypo-Prothrombinemia Produced by 3,3'-methylene-bis-(4-hydrox3’^coumarin)
and Its Use in the Treatment of Thrombosis, Science 96: 345, 1942.

G. a. Allen, E. V., Barker, N. W., and Waugh, J. M.; A Preparation From Spoiled Sweet
Clover [3,3'-methylene-bis-(4-hydroxycoumarin) ] "Wliich prolongs Coagulation and
Prothrombin Time of the Blood; a Clinical Study, J. A. M. A. 120: 1009, 1942.
b. Barker, N. W., Cromer, H. E., Hum, J., and Waugh, J. M.: The Use of Dicumarol in
the Prevention of Postoperative Thrombosis and Embolism With Special Eeference
to Dosage and Safe Administration, Surgery 17: 207, 1945.

7. Wright, I. S.: Experiences With Dicumarol in the Treatment of Coronary Thrombosis.

Proceedings Araer. Fed. Clinical Eesearch, first Far Western Meeting, Salt Lake
City, Dec. 28, 1945.

8. Baumgarten, P.: Entziindung, Thrombose, Embolie, und Metastase im Lichte neurer

Forscliung, Munchen, 1925, J. F. Lehmanns.

9. Dietrich, A.: Thrombose, ihre Grundlage und ihre Bedeutung, Berlin, Wien, 1932, Julius

Springer.

10. Hueck, H. : Blood Proteins After Operation, Arch. f. klin. Chir. 136: 774, 1925.

11. von Seemen, H.: Operation und Gewebeschonung: Beziehungen zwischen Operationswunde

und Entstehung, Vermeidimg und Bekiimpfung der mittelbaren Operation schiidigungen
(spontane Venenthrombose und Pneumonie), Deutsche Ztschr. f. Cliir. 223: 85, 1930.

12. Stuber, B., and Lang, K. : Zur Pathogenese und Therapie der Thrombose, Klin. Wchnschr.

9: 1113, 1930.

13. Naegeli, Th.: Postoperative Thrombosis and Embolism, Schweiz, med. Wchnschr. 55:

520, 1925. .

14. V. Seemen, H.: Quoted by Bruzelius (Ecf. 17), Verhandl. deutsch. Gesellsch. Chir. 51:

41, 1927.

15. Lbhr, W.: Quoted by Bruzelius (Eef. 17), Deutsche Ztschr. f. Chir. 183: 1923.

16. Starlinger, W., and “Sametnik, S.: Ueber die Entstehungsbedingungen der spontanen

Venenthrombose, Ivlin. Wchnschr. 6: 1269, 1927.

17. Bruzelius,' S.: Dicoumarin in Clinical Use, Acta chir. Scandinav. 92: Supp. C, 1, 1945.
IS. Flynn, J. E.: Personal communication.

,19. Winternitz, hi. C., Thomas, E. M., and LeCompte, P. M.: The Biology of Arterio-
sclerosis, Springfield, 111., 1938, Charles C Thomas.

20. Horn, H., and Finkelstein, L. E.: Arteriosclerosis of the Coronary Arteries and the
IMechanism of Their Occlusion, Asr. Heart J. 19: 655, 1940.

THK NEUROVASCULAR SYNDROME AS J\IANIFESTED IN THE

UPPER. EXTREMITIES

Colonel Ross Paull, M.C.

Arimy of the United States

O VER a period of many years much has been written on vascular and neuro-
logical syndromes which result from anatomic anomalies in the neck Jiiicl
shoulder girdle. It is not the purpose of the author to review the literature
dealing with these anomalies, nor to outline the differential diagnostic features.
Wright® has reeentlj' well provided this information in his article describing the
neurovascular syndrome produced bv hyperabduction of the arms (Pigs. I A,
IB, IG, and ID) in persons not necessarily having any anatomic anomalies in
the neck or shoulder, such as extension of transverse processes and cervical ribs
of the lower eeindcal verlebrae,^'^ tendinous or cartilaginous extensions or
counterparts of cervical ribs,® scalenus anticus,'’’ ® abnormal costoclavicular com-
pression,®’ ■ ruptured cervical nucleus pulposus, extrinsic or intrinsic tumor of the
conneal cord, ulnar or median nerve injury, etcetera.

This ease report describes a patient with complaints which, but for Wright’s
recent article,® would very probably have been diagnosed as “scalenus anticus
syndrome” only, while actually this represents an example of the “hyperabduc-
tion neurovascular syndrome” as well. This material is offered so that the latter
syndrome may be more frequently in examiners’ minds, more zealously sought
for, more frequently I'eeognized, and more properly treated. Certain observa-
tions and recommendations as to treatment may be worthy of consideration.
Relief from long-standing symptoms rapidly followed after the treatment out-
lined was initiated in this case. The I’clief may, however, have been unrelated
to or only iiartially due to the treatment.

CASE report

A white man, 52 years of age, of temperate liahits but for smohiiig two amt a half
jiacks of cigarettes daily, was unable to recall anj' illness, operations, oi injinics uc i nii,, i
have played a role in the precipitation of his pre.^ent illne.«s.

In Januaiy, 194.'{. while on Army transport duty he spontaneously and gradually de-
veloped a pain in the region of the distal anterior aspect of the right biceps muscle. ns
pain bccanie extremely severe. It was unaccompanied by tenderness, paresthesia, In post icsia,
numbness, or tingling. Passive or active motion of the right htimeroscaptilar and elbow joints
and pronation or supination of the riglit forearm greatly aggravated the pain. Aiiod^ncs,
heat, massage, and manipulation of the aforc-mentioned joints failed to relieve this pain,
Imt it gradually subsided, disappearing about April, 1942. In duly, 194.,, tlic pain spon-
tancously and gradually returned, this time bilaterally. It was not at this lime aggravated
by the motions which liad proved aggravating from .Taruiary to ..\jiril, ItM.,. He now ob-
.-.ened the pain to be angravate<l bilaterally by allowing Ids shoulders to be depressed toward
his hips while his arms were at Ids sides and to bo more distre.^sing at night than by day

litcelvctl for t>ubl lent Inn Xov. t. liii.*,.

32

I’AULL: NEUROVASCULAR SYNDROilE IN' UPPER EXTREMITIES

33

The pain was now, as before, essentially constant with fluctuations in severity. , It was par-
tially relieved if, while sitting, the patient placed his elbows on a table or on the arms of a
chair, and if, while lying prone, he allowed liis forearms to hang over the sides of the bed
toward the floor. His customary sleeping position had been the prone position with his
arms hyperabducted above his head and approximately parallel to tlie longitudinal axis of
the body (Fig. lA). Tlie symmetrical pains developing in July were from the onset accom-
panied by bilateral ulnar hypesthesia, bilateral median and ulnar numbness and tingling,
essentially constant pain in the left forearm and hand, and recurring episodes during which

34

AMERICAX HEART JOURNAL

liis left forearm felt cold. An extended course of generous doses of thiamine hydrochloride
parenterally administered elsewhere had failed to give relief. The persistence of severity
of the sjnnptoms resulted in his hospitalization April 30, 1945.

The physical examination on this date revealed: (1) Hypesthesia over the areas inner-
vated by the ulnar nerve, bilaterally; (2) obliteration of the right and reduction in amplitude
of the left bracliial pulse when the patient’s arms were actively or passively^ hyperabducted
(about 160 degrees) above his head when he was in the erect position (Fig. IC) ; (3)
obliteration of the right and reduction in amplitude of the left brachial pulse when the
patient rotated his head to the left or right, respectively, with his arms abducted laterally
90 degrees from Ids body (less extreme rotation of the head was required to obliterate the
pulses if the subject was obliged to rotate Ids head against the resistance of the examiner) ;
(4) the development, in about tliree minutes, of bilateral ulnar numbness and tingling on
the assumption of the positions portrayed in Figs. lA, IB, and 1C (this numbness and tingling
developed even with a degree of hj’perabduetion insufficient to obliterate the radial pulses
and regardless of whether the patient was erect, prone, or supine) ; (5) failure of the
brachial pulse to return for two to five seconds after the obliterating positions had been
abandoned, the interval increasing somewhat with extension of the time obliterating position
had been maintained; (6) the shoulder girdles to be lightly muscled and normally^ or suh-
normally free in shoulder elevation and in hyperabduction of the arms.

Active or passive extreme depression of the shoulders with the aims at tlie sides
failed to obliterate or reduce either bracliial pulse; passive forcing of the shoulders pos-
teriorward and domiward failed to obliterate or reduce the amplitude of either brachial
pulse.3-v Unfortunately', the author forgot to determine if prolonged depression of the
shoulders toward the hips or domiward and posteriorward would produce symiptoras. It would
seem likely, however, that symptoms would have resulted, for the patient stated in his history
that his arms and hands pained and tingled when permitted to hang at his sides when he
was in the erect position. This pain and tingling was very favorably influenced by removing
the weight of the upper extremities from his shoulders by' resting his elbows on a table or
the arms of a chair. No reflex changes were demonstrable. Oscillometric and surface
temperature studies were not available.

X-ray' studies of the cervical and thoracic spines revealed only' a slight scoliosis in the
region of the fifth thoracic vertebra, with the concavity to left. X-ray studies of the sinuses
revealed a raarked uniform density througout the left antrum.

The blood count, blood Kahn, blood sedimentation rate, blood ure.a nitrogen, urinalysis,
and x-ray' studies of the heart and lungs were normal.

The symptoms and findings lead the examiner to the conclusion that the patient probably
had both the scalenus anticus syndrome^, c and the “neurovascular syndrome produced ])y
hypcrabduction of the arm.s, “s described by' Wright. The amount of vascular element in
the clinical features of this particular case is difficult to evaluate, for the brachial plexus,
bilaterally, reacted to hyperabduction of a degree insufficient to obliterate the brachial
pulses, and bilaterally reacted with the dcvelopmcni of .“ymptoms when the arms hung at
the sides with the patient erect, though even an extreme of this latter position failed to
obliterate either radial jmlse. This case .seemed not involved by the presence of a cervical
rib. Whether or not a tendinous or cartilaginous band in the place of a rudimentary
cervical rib was pre.sento and acted in the manner of its counterpart was not determined;
that it was the chief causative factor appe.ared unlikely. A ruptured cervical nucleus pulposus
could possibly lie pre.scnt and causative; this, too, appeared unlikely in the absence of x-ray
evidence of such a condition. Wrights reported that the obliteration of the radial pulse by
hyperabduction of the arms is difficult and frequently' impossible to produce in “loose
jointed ' ’ individual-.

Since stretching or ten.-ion of the nerve trunks and brachial plexus is among the i) 0 ssible
cau'-c.s of the symptoms under study, it was decided to direct the patient to practice certain
e'terci.«es and maneuver.^ which, it was believed, would possibly' slowly lengthen the nerve and
xu'jcntar .‘•trnctures, thus reducing the amount of tension to which they would be .subjected and

PAULL: NEUROVASCULAR SYNDROME IN UPPER EXTREMITIES

35

THE

NEUROVASCULAR
SYN D ROME
PRODUCED BY
HYPERABDUCTION
OF THE ARMS

Phrenic nerve
Scalenus M.

Brochial plexus
Coracoid pro.
Subclavian arl'^^

Pectoralis min^M.

Fig. ID.

ARsAA IN
RELAXED
ABDUCTION

Scalenus M.-med.-f anh
Brachial plexus
Phrenic nerve
Subclavian ar

Pig. IE.

Pigs. ID and ID. — These figures are included for more grapliic exhibition of anatomic relation

ships in various positions.

at' AMERICAX HEART JOURNAL

\\oiikl make the patient’s shoulder giidles more “loose jointed.’’ By sti etching out the mus
culofascial structures -uhicli limit the excursion of the lateral angle of the scapula toward
the midline of the body and cephaladj one reduces the acuity of the angle around which nene
and vascular structures are stretched as they pass under the coracoid piocoss when the
subjects ’s arms are hyperabducted. This same stretching would also tend to widen the
costoclavicular space. Tlie maneuver outlirred to relieve the mtolerarrce to the hyperabduc
tion position consisted simply of the patient’s suspending himself by closely apiiroximated
hands while he relaxed his shoulder girdle muscles (Fig. 2). He was to so suspend himself
tluee or four time a day for such a perrod of time as comfort permitted. To build up the
antagonists of the muscles we sought to stretch, the patient was directed, three oi four
times daily, while erect and with a 10- to 20-pouiid weight in each hand, to shrug or derate
Ins shoulders (Fig. 3).

' i

FIfr. 3.

I^lK. 2— The position of suspension of Uio hotly bv clo^-oly apiuoximated liantK. while
shouUler Kirtllo niu'-rlcs aie relaxed as completely as comfort permits.

Fin. a. — The position of ‘‘sliruacinir” or cleratluK the shoiiUUis afraln*-t welirlited leslst-
.inee. The viioulder.s aie attKclv elevated and passively lel.ixed or depressed alternately,
llunby d>\clopiim the elevatoi.s of the shouldcr.s, better cquippinw them to hold the points of
tli>‘ shoulders hiyhi_r witliout conscious effort.

If ihi- patient’s shoulders could lie raised by developing the elevators of the shoulder,
the neuity of the angle of the neurovascular structures as they pass tiirougli the angle
formed by the first nb and the sealeiius anticus muscle would be reduced. Tliis should, it
was believed, reduce tlie irritation to these structures at this musculoskeletal angle. Elevation

PAULL: XECTOVASCUriAH SYNDIJOAfE IN UPPER EXTREAIITIES 37

of tlic shoulder Avould also increase the costoclavicular space, lessening the hazard of pincliing
neurovascular structures at this point. These maneuvers and exercises vere initiated about
A [ay 32 and were continued after the patient’s discharge from the hospital, May 18, 1945.
The ])atient was also directed to change his sleeping position to one in which his arms were
not held in hjnerabduction (Fig. 1^).

He reported improvement at the time of discharge, and on June 22, 1945, wrote, ''My
shoulders feel much better since taking the 'chinning’ exercises. There is no pain in my
left arm or hand. You will recall that when I was in the hospital, that was where I was
bothered most. I still get the tingling sensation in the fingers in certain positions. My right
wrist and right hand have bothered me and that appeared to be brought on by the chinning
exercise. I appreciate the advice wliieli I received about the shoulder exercises. I am
continuing the exercises.” About June 25 he reported by phone that the pain in Iris right
wrist and hand had disappeared. On Sept. 1, 194.5, the patient returned for re-examination.
He then reported that the disturbing sjunptoms had disappeared and had not returned; that
he had had no numbness or tingling in either arm or hand since about July 1; and that the
pain earlier reported in the right wrist and hand stiU tended to recur infrequently, to last
but a few days, and to develop and disappear gradually. The physical findings, September
3, were similar to those found April 30 on admission to the hospital except that the bilateral
ulnar lij'pesthesia liad disappeared and the shoulder girdles seemed more "loose jointed.”

During liis hospitalization in May, 1945, this patient exhibited keen interest as to the
possible causative mechanisms and our aims in having him follow our suggested schedule of
Ireatment. He has now quite completely abandoned his once customarj- sleeping position
(prone, wdth his arms in hyperabduction, Fig. lA), and he now subconsciously rests his elbows
on a table or chair arms when feasible. His new sleeping habits, his faithful exercise of
the outlined treatment, or a combination of influences, some of which may not be clearly
understood, may have produced the relief. This has occurred in spite of the persistence of
certain physical findings which at the time of hospitalization seemed significant.

DISCUSSION

■WHiile the symptoms experienced by thi.s patient probably resulted in part
from obliteration of the arterial blood supply to the ai-ms, it seems likely, in
view of the prompt development of tingling in the fingers even when the arms
were hyperabducted to a degree insufficient to obliterate the radial pulse, that
changes in the nerve trunks resulted from prolonged stretching, pinching, or
local ischemia, or some combination of these three factors. This does not, how-
ever, preclude the participation of arterial occlusion in the damage to the plexus
and nerve trunks, for this patient’s sleeping habits were such that he probably
had pulseless brachial arteries for rather extended periods during his sleep.
Tie habitually .slept in the prone position and many, if not most, prone sleepers
.sleep with their arms in a position of hyperabduction and their faces turned
toward one shoulder.

The obliteration of the brachial pulse by either the scalenus anticus .syn-
drome or the hyperabduction .syndrome may be due to either actual compression
of the vessel so that its walls are opposed and lumen obliterated or to iiTitative
spasm of the vessel. The fact that the radial pulse after obliteration does at
times fail to return immediately on removal of the obliterating position or
maneuver .sugge.sts that the latter is operative at times. Thi.s may explain
Wright’s observation® that certain positions of the arm, though unchanged, are
accompanied by sudden changes in the pre.sence or absence of a palpable radial
pulsation.

38

AMERICAN heart JOURN^VL

This case demonstrates that, in the same person, several variations in the
mechanisms responsible for irritation or damage of neurovascular structures of
the neck and axilla may exist. This individual is believed to have both the
scalenus anticus and the hyperabduction sjmdrome, each syndrome possessing
identical or very similar symptoms but produced by different means. The
fomier syndrome is produced by the irritation and/or obliteration of neuro-
vascular structures at the angle formed by the attachment of the scalenus anticus
muscle to the fii’st rib, the latter sjmdrome bj’- abnormal costoclavicular compres-
sion, or by toi’sion, tension, or compression of the neurovascular structures at
the point where they pass under the coracoid process and posterior to the pec-
toralis minor muscle, or by both mechanisms together.

SUMMARY

1. Neurological and vascular syndromes, singly or combined, caused by
various anatomic anomalies and changes in the neck and shoulder region, have
long been recognized. Similar or identical syndromes, caused by a functional
mechanism (hyperabduction of the arms) in the absence of anatomic anomalies
have more recently been recognized and described by Wright.®

2. The recently reported, functionally produced syndromes® appear to be
commonly reduced (1) at the point where the vessels, plexus, and nerve trunks
pass between the clavicle and fii*st rib by costoclavicular pinching of the tra-
vei-sing structures, and (2) at the angle around which these stmetures pass
under the coracoid process and posterior to the pectoralis minor, by torsion or
stretching of the neiuovascular structures. (Arterial spasm from irritation
ma}’’ in some eases contiibute to the obliteration of the brachial pulse.)

3. Nonsurgical therapeutic suggestions, offered for consideration, are de-
signed to: (a) avoid the positions responsible for the syndromes when prac-
ticable; (b) widen the costoclavicular space; (c) lengthen the involved neuro-
vascular stmetures; (d) reduce the acuity of the angle these structures travei’se
as they pass under the coracoid process while the arms are hyperabducled; and
(e) shorten the course traversed by these structures.

REFERENCES

1. Willsliire: Referred to in Clinical Records, Supernumerary Fiist Rib, Lancet 2: 03.5, 1800.

2. Jones, F. W.: On the Relation of the Limb Plexuses to the Ribs and YcVtebral Column,

J. Anat. & Physiol. 44: 377, 1910.

3. Murphy, Thomas: Brachial Neuritis From Pressure of the First Rib, Australian M. J.,

15: 5S2-5SO. 1910.

4. Howell, C. M. H,: A Consideration of Some Sjunptoms Which May Bo Produced by

Cervical Ribs, Lancet 1: 1702, 1907.

5. a. Naffziger. II. C.: Editorial: The Scalenus Svndrome, Surg., Gj-ncc. & Obst. 64: 119, 1937.
b. Naffziger, 11. C., and Grant, W. T.: Neuritis of the Brachial Plexus, Mechanical in

Origin; The Scalenu.« Svndrome, Surg., Gynec. & Obst. 67: 722, 1938.

(5. Craig, W. AIcK., and Knopperl Paul A.i Cervical Ribs and the Scalenus Anticus Syndrome,
Ann. Surg. 105: 550, 1937.

7. Falconer, Murray A., and Weddell, Graham: Costoclavicular Compression of the Sub-

clavian Arteiy and Vein, Lancet 245: 5.39, 1943.

8. Wright. I. S.: The Neurovascular S\mdrome Produced by Hyperabduction of the Anns,

Am. llr.ART J. 29: 1, 194.5.

POTENTIAL VARIATIONS 01’ THE RIGHT AURICULAR AND
VENTRICULAR CAVITIES IN I^IAN

Hans H. Hecht, M.D.

Salt Lake City, Utah

I N THE five cases which form the basis of this report, an attemiit was made to
trace the coni’se of the action current of the human heart directly by means
of intraeardiac catheterization. This seemed desirable because some of the
fundamental concepts of electrocardiography have been evolved primarily from
pertinent animal experiments, and assumptions concerning the course of the
action current in the human heart have been made merely b}" analogy. Brieflj^
any electrical current of action can be considered as a line or layer of electrical
dipoles or doublets so arranged that electropositive forces (source) are immedi-
ately followed by electronegative charges (sink).^’^ To electrical currents pro-
duced by the heartbeat, the laws which govern their fiow in volume conductors
have been applied,^ It has been demonstrated that electrograms recorded from
auricular muscle strips or from muscle in situ follow closely a predictable pat-
tern based on formulas derived from such laws.^**

The spread of impulses over and through cardiac muscle seems to be very
similar in practically all species regardless of the presence of readily demon-
strable conducting tissues,® Presumably no striking differences exist between
the spread of the action current in the human heart and in the hearts of other
mammals. The clinical use of precordial leads, for example, is based on the es-
sential similarity in that respect of experimental electrocardiograms, particu-
larly those of dogs, to those of man. For the study of the detailed sequence of
activation of auricular and ventricular heart muscle, records from the endo-
cardial as well as from the epicardial surfaces are required. Many such studies
have been reported since the early observations of Lewis® and Lewis and Roth-
schild.’’ The admixture of cavity potentials to the precordial and standard limb
lead electrocardiograms of the dog has led to newer interpretations of the pat-
tern of bundle branch block, myocardial infarction, and myocardial infarction
complicated by bundle branch block.®’’® Again by analogy, the results of these
observations on animals have been used in the interpretation of the abnormal
human electrocardiogram.”’ ” Epicardial leads have occasionally been recorded
from human hearts but the potentials from the auricular and ventricular cavities
needed to provide the final proof of the similarity of the human action current
to that of experimental animals are lacking. It has been suggested that unipolar

Read in part before the Annual Meeting of the American Federation for Clinical Re-
search, Atlantic City, May 28, 194 G.

Part of this investigation was supported by grants from the Fluid Research Fund of
the Rockefeller Foundation, the Utah Copper Company Research Fund, and the Physicians’
Research Fund of the University of Utah Medical School.

Received for publication Sept. 21, 1945.

*From the Department of Internal Medicine, University of Utah Medical School, and
the Wm,' J, Seymour Hospital, Eloise, Michigan.

39

40

AMERICAN HEART JOURNAL

records from the right aim (Vr) and from certain esophageal leads I'cllecl
\-ariations in eavitj' potentials. Leads of this land are taken from positions
located approximately opposite the large vascular openings at the base of the
heart. This peimits the potential variations of the ventricular cavities to he
transmitted to the right shoulder and the right aim, or to the esophagus.*-’®
The location of these leads ivitli respect to cardiac muscle is such, however, that
t hey cannot be expected to represent potential variations of purely intracardiac
origin.

Cardiac and vascular catheterization through the anteeubital veins, as prac-
ticed by Cournand and others, provides a relatively safe procedure for obtain-
ing electrocardiograms from the right auricular and ventricular cavities and
from the larger veins.*® In the following experiments a No. 9 radiopaque
catheter Avas used through which a small enamel-coated copper vure was threaded.
The end of the vure was soldered to a small lead pellet which fitted and all but
completely occluded the small opening at the tip of the catheter. This unit
constituted the exploring electrode. A central teiminal Avas used as the indif-
ferent electrode. Under local infiltration Avith noAmeain, a right or left ante-
cubital vein, usually the basilic A’ein, aa’us exposed. Under fluoroscopic control
the catheter A\'as inserted and gently pushed ahead until the tip of the electrode
Avas found to lie in the desired position. The patients AA^ere given sedation.
Those in cardiac failure receiA'ed 0.5 Gm. of aminophylline intravenously prior
to the exposure of the cubital Amn. All patients receiA’ed 25 to 50 mg. of heparin
to lessen the chance of intraAmscular clotting. None of the patients complained
of pain or of discomfort of any kind, even Avhen the tip of the electrode aa’RS
seen to rest against cardiac muscle. No reactions or aftereffects Avere en-
countered. All patients reeeiA’-ed prophylactic treatment AAutli sulfadiazine for
tAvo days after the procedure. X-rays and electrocardiograms Avere recorded
frequently and at regular intervals.

The present report deals AAdth the results obtained in Aa^c subjects. There
Avere tA\-o instances of right bundle branch block (one complicated by a myo-
cardial infarction tAA’o years preAuously), one of left bundle branch block, one
of left ventricular enlargement, and one instance of left A’cntricular enlarge-
ment with frequent auricular and A'entricular extrasystolcs (bigeminus). On
all patients standard bipolar limb leads, uni]iolar limb leads (extremity po-
tentials), and serial unipolar preeordial leads Avere ol)tained either immediately
liefore or after the procedure. In one instance serial esophageal leads Avere
recorded. Simultaneous records of cither Lead I or of preeordial Lead Vj Averc
made Avhenever feasible.

The records may conA’cniently be di.scussed according to the location of the
lip of the electrode as detennined by fluoroscopy.

Superior Vena Cava . — In tAvo imstanccs a j-ecord was obtained before the
(‘lectrodo had entered the heart itself. Both AA-ere patients Avith considerable left
ventricular enlargement (one Avith associated signs of left auricular distention).
The records 'revealed primary negatiA’o deflections for P and QPS, Avith positive
T Avave_s. q'he P AA-ave.s Avei-e approximately one-half the size of QP.S complexe.s a
and Avere duuble-not<‘lie<l in both instances, c.specially .so in the case slioAving

HEGHT: POTENTIAL VARLITIONS OF RIGHT HEART IN AIAN 41

evidence of auricular enlarg-ement. The size of the deflections was of the order
of those nsnally seen in unipolar extremity potentials, and their shape was al-
most identical with that observed in unipolar right arm leads (Fig. 1).

Inferior Vena Cava . — In one instance the electrode slipped into the inferior
vena cava and down into a heaptic vein. The potentials recorded from tlie
inferior vena cava were similar to those obtained from the superior vena cava,

Pig. 1. — Leads I, II, and III, unipolar extremity potentials (Vr, Vl, Vf), and leads from
superior vena cava (A^sro), inferior vena cava (Vivo) and from a hepatic vein (Vnv).
Galvanometer sensitivity normal for standard lead and extremity potentials (augmented
type), 0.75/N sensitivity for venae cavae and hepatic vein leads.

except that the auricular deflections were more rounded and the ventricular
complexes lacked a small R wave which had been present before (Fig. 1). The
record from the hepatic vein was cpiite different. A biphasic P wave was ob-
tained, with a large slurred positive limb and a small negative spike. The
ventricular deflections, were primarily po.sitive, displaying large R waves pre-
ceded by Q waves and followed b.v a small S deflection. The T waves were posi-
tive (Fig. 1). Neither the auricular deflections nor the ventricular complexes
resembled those recorded in standard leads, extremity potentials, (unipolar liml)
leads), or in any of six precordial leads. Tliey were, however, of the left ven-
tricular type, with a delayed peak of R (late onset of intrinsicoid deflection).
The record appeared similar to those recorded by Helm, Helm, and Wolferth^''
from the duodenum.

Right Auricle . — ^^^ith the exception of the case mentioned above, the
electrode entered the right auricle proper in all instances and records Avere ob-
tained from various auricular levels.

1. Auricular Deflections: The auricular deflections appeared similar in con-
figuration to those obtained from esophageal leads at auricular levels and were

AMERICAN HEART JOURNAL

42

of the same magnitude or slightly larger. Endocardial auricular waves are
always biphasic and display a distinct QRS t^^pe of deflection, and are often
followed by a plainly visible auricular T wave.® In one instance the electrode
was found to be located inside the right auricle, adjacent to the entrance of the
superior vena cava. A lai'ge, completely negative deflection was recorded (Pqs),
indicating that the electrode very likely wms located at the region of primary
negativity, the sinus node (Pig. 2, A). When the electrode wms moved toward
the junctional region, tliere appeared a small Pr wave wdrich gradually increased,

m ©

i'"''' il i'

Fig. 2. — Case of right bundle branch block. (0.5/N sensitivitj’.) A, Large negative
auricular deflection recorded from the immediate vicinity of the sinus node. B, Position of
the exploring electrode slightly lower than in A.* a small Pa wave has appeared, total voltage
of P has decreased. Onset of intrinsic deflection for P occurs 0.005 second after beginning
of Pgns. C, Low auricular position (junctional region) : small P wave with broad Pa deflec-
tion, Onset of intrinsic deflection for P: 0.060 second after beginning of Pgns. Note change
m contour of the ventricular deflection when the electrode is moved from upper to lower
auricular levels.

so that at lower auricular levels a bi'oad Pr, followed by a small sharp Pg de-
flection, was present (Pig. 2, B and C). A small Pr with a relatively large Ps
■was always noted in other records whenever the electrode was located in the
upper auricular region (Pigs. 3, C, 4, E, and 5, A). Occasionally the Pg deflec-
tion was broad: at times it completely occupied tlie space between the end of
P and ithe beginning of QRS, which is usually isoelectric in standard limb leads
(Pig. 3,(7). Large P deflections with small or absent Pr are cliaracteristic of
upper auricular levels; large Pr waves w'illi a* decrease in the total voltage of
P are tyiiical of lower auricular or junctional levels. These findings are in agree-
ment with those of IMacleod and Cohn,^' who obtained endocardial leads in cats
with a comparable technique. In one instance a biphasic P wave with a pre-
dominant Pr deflection Avas obtained when the electrode Avas situated in the
vicinity of the tricuspid valves (Pig. 4, C). When an attempt AAms made to in-
sert the electrode into the right A'entricle, the electrode curled up and Avas finally
found lying along tlie auricular .septum, apparently in contact AA'ilh the endo-
cardial surface. A .strikingly large biphasic auricular deflection Avas obtained

'Since tlic .>.nape of the iiction current.s recorded from tiie auricle.s doc.s not appear to
differ fundamcntaliy from the siiape of action currents recorded from the ventrlcle.s, it seems
advisable to use a companible nomenclature. Therefore. folIowinR' the .standard nomenclature
for QUS. tlm terms Pq. Pqv. Pons, Pe. Ps and Pr have been introduced to facilitate tlie dc-
.scrlptlon of the eomplexes othained.

In tliis pajier. tiie auricular T wave is labeled Pr. instead of T. as lias been .suKKCsted.

I T seems to 1 mi a mor<‘ io.dcal term than T, the derivation of whicli may not be re.adiiy
miclerstood.

Tlie use of the terniinoloio' wlitcii i.s hero propo.sed does not imply timt the xpretul of tlie
action current tiirmi^-ii auricular muscle is similar to tlie .spread over the ventricular nnis-

HECHT : POTENTIAL VARIATIONS OP RIGHT HEART IN MAN

43

Fig. 3. — Auricular and ventricular extrasystoles. (O.-'i/N sensitivity.) A, Case of right
bundle branch block (see Fig. 2), endocardial lead from the sinus regions. Deep Pqs deflec-
tions Avith sinus extrasy.stole (second beat) showing aberrant auricular response. S, Case
of left ventricular enlargement. Uppei- auricular or lower superior vena cava lead. Beats 1,
3, and 5 are normal rc.sponses Avith deep QS deflections ; Beat 2 is a left ventricular extra-
.sy.stolc (Avith lai-gc S Avaves in Lead 1 — not shoAA’n). Q wave transmitted from left ven-
tricle, large R AvaA'es from I’ight A'entricular cavity. Beat 4 is an auricular extrasystole
AvIth abnormal p avpa'c and a broad QS deflection (right ventricular cavity). C, Same
case as B. Endocardial lead from upner auricular leA'el. The third beat is a normal com-
plex Avith a small Pa, deep Ps, and deep QS deflection. Beat 1: Auricular (nodal?) extra-
sy.stole with short P-R interval, abnormal P, and deep QS. Beat 2 : Left ventricular extra-
systole Avith largo R (right ventricular cavity). The small "S AvaA'e” appears to be the
ftnal portion of a Pgis.s superimposed upon a A'entricular complex. Beat 4 represents again
a left ventricular extrasystole Avith a Pons immediately preceding it. The early part of QRS
is superimj)osed upon the ascending limb of Ps.

4 . — 4_ B, and C: right bundle branch block. D. E, and F; left bundle branch block.
A, Lead I and Vn (2/N sensitivity). B, Lead I and electrogram from right auricle (0.9/N
sensitivity). Arrow points to small preauricular deflection. Note Pt distorting the* P-R
interval. O, Lead I and endocardial lead from loAver auricular leA-els (0.9/N sensitivity).
Some distortion by artifacts. D, Lead I and Vn (2/N sensitivity). E, Lead I and endo-
cardial lead from upper auricular leA'el. Note preauricular deflection and small Pn. F,
Lead I , and , endocardial lead from right A'entricle (0.15/N sensitivity). ArroAV points to
small preintrinsic deflection of QRS.

AiMERICAN HEART JOURNAI.

44

which displayed a classic intrinsic deflection. Its onset appeared 0.065 second
after the beginning of the auricular deflection (Fig. 4, 5). In this case, high-
speed records revealed a small, positive preauricular deflection immediately
preceding the onset of Pr and oceun-ing almost 0.05 second before the onset of
P in a simultaneously recorded standard bipolar lead. A -similar deflection was
found in one other instance (Pigs. 4, E, and 5, A).

Auricular extrasystoles showed either increased or decreased Pr deflections,
when compared with the pattern of the normal beats for that region. A shins
extrasystole recorded with the electrode placed at the sinus region shoAved a deep
but splintered Pqs deflection (Fig. 3, A).

2. Yeniriculm' Deflections: Records from loAver right auricular levels, taken
AAuth the electrode in the vicinity’- of the tricuspid valves (beneath or just to the
right of the sternum), should represent potential A’^ariations of the right ven-
tricular cavity AAdiich Avere transmitted through the atrioventricular opening.
At higher auricular levels, the electrode is situated behind and above the ven-
tricles and may conceivably deflect a mixture of potential variations of the right
and left A^enti-ieular cavities and of endocardial action currents from both ven-
tricles. A strilring similarity Avas always noted betAveen ventricular complexes
recorded at high auricular IcA’-els and those recorded in a unipolar right arm
lead (Vr) . These records usually differed from those obtained from loAver au-
ricular or A’entricular levels, particularly Avhen bundle branch block Avas present
(Figs. 1, 4, and 5).

The tAvo indiAuduals AAutli nonnal ventricular activation (left ventricular
enlargement) displayed deep Q-S deflections from all auricular levels, folloAA’Ccl
by small, positive T AA^aves, often AAutli slight elcA’ation of the S-T segment (Figs.
1 and 3, B and C ) . In left bundle branch block a somoAvhat similar record Avas
obtained. The QRS deflection aa’cs represented as a deep negative deflection
throughout ventricular excitation, except for an earlier jAortion partly pi’eeeding
the beginning of QRS in a simultaneously registered Lead I. The record dis-
])layed a small Q and a small R, folloAvcd by a broad and notched S (Figs. 4, E,
and 5. A) . The duration from the beginning of Q to the top of R measured 0.055
.second; the S AAmve from the top of R to S-T .inaction, 0.125 second. The total
duration of QRS in the standard limb Lead I mca.sured only 0.165 second; in
endocardial loads the dAiration of QRS AA'as O.ISO second.

Records taken from the upper auricular Ica’cIs of the Iavo subjects Avitli right
bundle branch block AA'orc similar in most details to those obtained from the right
arm of those subjeets (P^igs. 2. A and B, 3, A. and 4, 7>). In the first case a
small R Avave pi-cccded a ra])id doAvmvai-d deflection, after Avhich a broad,
notched R' avoa'c occurred AA'hich occupied more than half the total duration ot
QRS (Figs. 2, -1 and B, and 3. A). The small R Avave Avas not present in a
record taken from the lower auriculai- loA-el, and a short hut deej) Q Avavc Avas
noted, folloAvcd by a slightly notched R deflection. The ])eak of R appeared
0.04 second eai’lier than in upper auricular recoials (Fig. 2, 6'). In the second
ca.se a similar difference was noted : the record taken from the po.stei-ior a.speets
of the auricle AViis similai- to Yr and displayed a small Q Avavc folloAvcd by a
broad and notched R Avavc f l-^ig. 4, B). The complexes taken in the vicinity of

HEGHT; POTENTIAL VARIATIONS OP RIGHT HEART IN MAN 45

tlic tiiciispid valve showed a siaall a deej) S, a large and a small In

tills case, the pealc of li occurred later than that of It in upper auricular rec-
ords (Fig. 4, (7).

Frequent ventricular extras.ystoles were noted in one case. Because the
extrasystoles displayed a conspicuous S wave in Lead I, they were thought to
have arisen within the left ventricle. Both iqiper and loiver right auricular
records revealed large positive deflections without a trace of Q or S weaves. Pre-
inatme auiicular extrasystoles without aherrant ventricular responses aLvays
displayed a conspicuous downward ventricular deflectibn (Pig. 3).

Right Yentricle . — In one patient with left bundle branch block, the right
ventricle was entered and the tip of the electrode w-as found to be located to the
left of the steiaiurn, in the apical region. The voltage of QRS w^as about eight
times higher than that observed in the auricles, wliile the P waves all but dis-
aiipeared and became quite similar to the small, rounded deflections usuallj^ seen
in standard limb leads and in precordial leads (Pig. 5, B). The ventricular
deflections seemed to be primarily negative, but a small, diminutive B wave
wms noted wliich sliowmd some phasic variation in height. On the average, the
top of the R wmve wms recorded 0.003 second after the beginning of QRS. The
R wave wms follow^ed by a deep and notched S deflection comprising almost the
entire time of QRS. A large positive T wave follow^ed. The downstroke of S
coincided with the rise of R in a simultaneously recorded precordial lead Vj.
A large, positive T wave wns recorded, its peak preceding the peak of T in the
precordial lead (Fig. 5, R). The intrinsicoid deflection (top of R) in oc-
curi’ed 0.022 second after the beginning of the activation of the endocardial sur-
face. Considering the approximate thiekne.ss of the right ventricle to have been

46

AMERICAN HEART JOURNAL

5 nun. (slight liypertropliy) in. this case, the speed of the action current tlirougk
the ventricular wall would have been about 300 mm. per second.

DISCUSSION

The studies which have been presented can be regarded only as preliminary
observations which need further amplification. However, some of the records
wliich were obtained strongly support our present concepts of cardiac excitation.
In this respect, three observations are of particular interest. (1) Large, pre-
dominantly negative auricular deflections are encountered at liigli aurienlar
levels, and distinct Pr waves aiipear either wlien auricular extrasysloles are en-
countered or when the electrode is moved toward the junctional region. (2) Yen-
trieular complexes from the junctional auricular region show negative deflec-
tions in a normally activated heart and in left bundle branch block, and show
positive deflections in riglit bundle branch block and in left ventricular extra-
systoles. (3) Ventricular complexes recorded from higher auiacular levels dif-
fer from those taken at loiver levels and from the right ventricular cavity.
They are quite similar, limvever, to those which are obtained when the exploring
electrode is placed on the right am (Vr).

Auricular Activation. — The finding of an area of primary negativity in
the vicinity of the opening of the superior vena cava is in keeping wdtli Lewis’
obseiwation on tlie location of the cardiac pacemaker in dogs.® The absence of
an early Pr wave is also noted in records taken from the venae eavae (Pigs. 1
and Z, B), but the sudden and strilung increase in magnitude of the deflection
in the case illustrated in Pig. 2 favors the assumption that the exploring elec-
trode must have rested close to a point which remained throughout the auricu-
lar ej'cle electronegative with I’espect to the surrounding tissue. 'Wliatever
theory is accepted, the region from Avhich the impulse originates must always
be negative to adjacent muscle. If it is assumed that the spread of the action
current is eliaracterized by a crest of positive charges immediately followed by
a negative Avalie, the region responsible for the release of impulses must always
face the electronegative Avake. This region aaIH neA-er become posit iA'c Avilh
respect to other parts of the cardiac muscle, and an electrode placed near this
region AAdll never record a positiA^c deflection unless the point of im])ulse fonna-
tion has .shifted. For this reason it can be a.ssnmed that the record obtained
represents the potential A’ariations of the sinus region.

A premature beat arising from this region (a sinus extrasystole) may at
times find part of the auricular muscle still refractory; under these conditions
an aberrant response of auricular tissue in the face of an othenvi.se noi-mal
actiA'ation A\nll be obtained (Fig. 3, A). This should result in an abnormal P
Avave in standard limb leads. For standard limb lcad.s, a sinus oxtra.systole is
defined as a premature complex AA'hose individual component.s, including P, are
identical Avith the sinus beats. This statement .should be modified, as an ab-
nonnal P might be expected to occur in .standard limb leads if the ucav impulse
falls in the recovety phase of the preceding bent. Unfortunately no simul-
taneous record.s of .standard loads were made in the example shoAA’u in Fig. 3, A.

HECHT; POTENTIAL VARIATIONS OP RIGHT HEART IN AIAN 47

Wlieii the electrode is moved away from the point of primary negativity,
a small Pr wave can be recorded which gradually increases in size. The pre-
ponderance of Pr over Pg increases with the distance of the exploring electrode
from the sinus region. This observation favors another concept of auricular
activation, which maintains that, in contrast to the manner of activation of ven-
tricular musculature, tlie auricles are activated radially from the primary point
of stimulation, similarly to tlie radial .spread of waves emitted bj^ a radio sender
or by a stone thrown into a lake. The auricular electrogram which was re-
corded in one instance (Pig. 4, P) differed in no way from many experimental
records obtained from isolated auricular mirscle strips of the frog or turtle,^’ •* or
from the epicardial auriculai- records of the dog obtained in situ.^ The similar-
ity of the P-wave pattern in certain esophageal leads to that in auricular endo-
cardial leads is quite striking, and was noted liy Maeleod and Cohn.^" In any
type of auricular muscle tissue no e.ssential difference between endo- and epi-
eardial records can be expected if the action current spreads radially from its
point of origin. Botli tjqies of records (endocardial and esophageal) can be con-
sidered as leads taken from a simple sheet of muscle submerged in a conducting
medium. Tlie intrinsic deflection for Pr appears later in esophageal leads than
in endocardial right auricular leads. This indicates merely that the distance of
the exploring electrode from the point of primaiy negativity is greater in
esophageal leads than in right auricular endocardial leads.

A small, rounded, positive deflection which definitely preceded any other
evidence of auricular activation was occasionally recorded (Figs. 4, B and E,
and 5, A). This “preauricular deflection” may be a nonnal constituent of the
human electrocardiogram which, because of its smallness, has hitherto escaped
detection in the conventional leads. Its significance is doubtful but it resembles
in contour and magnitude, though not in direction, the ‘‘prepotentials” which
have been recorded by Bozler under a variety of conditions. Bozler believes that
these potential oscillations might initiate normal sinus discharges.'®

Ventricular Activation . — No similarity of the electrocardiographic pattern
is present when the ventricular complexes from the endocardial surfaces are
compared with “epicardial” leads from the precordimn or from lower esopha-
geal levels. Deep Q-S deflections are obtained from the right auricular and
ventricular cavities when conduction of impulses occurs over the intact His
bundle either in normal sinus beats or in auricular extrasystoles with normal
ventricular responses. This again is in agreement with Maeleod and Cohn's
observation,^^ and with open-ehe.st experiments on animals where a needle
electrode is thrust through the musculature into the ventricular cavities.® On
the basis of these experiments, the characteristic Q waves of myocardial infarc-
tion have been, explained as denoting the appearance of potential variations of
the ventricular cavities at the epicardial surface which are transmitted through
electrically inert infarcted and fibrosed areas.®- The demonstration of
cavity potentials of a .similar kind in man makes the explanation of QRS. changes
associated with myocardial infarction directly applicable to human records.

The small, quite variable B wave noted at the beginning of QRS inside
the right ventricular cavity in a case of left bundle branch block is of interest.

48

A:\IERrCAN' HEART JOURNAL

The peak of this deflection occurs 0.003 second after the beginning of ventrieii-
lar excitation and precedes considerably the onset of QKS in simultaneous stand-
ard leads (Figs. 4, F, and 5, 15). A small preintiinsic deflection of this kindiias
been previously recorded in animal electrocardiograms from tiie right ventricn-
lar ca^^ty.®’ In Wilson’s record this deflection disappeared after left bundle
branch block was produced. This experiment indicated that with a normally
conducted impulse the left side of the septum was activated slightly in advance
of the right. For the curves presented by Wilson, Hill, and Johnston, and
also for those reported b.y Maeleod and Cohn, this explanation appears logical
and is slronglj’ supported by reports of vector analysis of standard limb leads
in human records.^”’ The mode of activation of the intraventricular septum
apparently varies, however, and in a number of records from various animals,
activation of the right ventricle was found to precede slightly that of the left.'
In the record presented in Figs. 4, E, and 5, B, left bundle branch block was
present, and activation of the septum must have occurred from right to left.
Consequently the deflection cannot be ascribed to early activation of the left
ventricular side of the septum. The assumption of Maeleod and Cohn,’" that
E waves of this Idnd from the right ventricular cavity may be caused by the
expanding polarization of the left ventricle after the activation of the right
has been completed, appears unlikely on anatomic grounds, since it assumes that
the long axis of the left ventricle exceeds that of the right to a considerable
degree. At present no satisfactory explanation can be offered for this small
preintrinsie deflection unless it represents activation of parts of the endocardial
surface at the base of the right ventricle, and of papillary muscles. These areas
are presumably activated after the activation of the apical region. The action
current .speeds from apex to base during the extremel.v short period of radial ex-
citation of the endocardial surface; this may account for a small period of posi-
tirity similar to the much longer period of positivity found in auricular muscle.

Except for the gi’eater width of the complexes, there is no essential differ-
ence in the activation of the right ventricle in normally activated liearts and
in those displaying left bundle branch block, since polarization of the right
ventricular cavity is not influenced by the altered activation of the left. The
right ventricular endocardial electrocardiogram obtained in the ease of left
bundle branch block (Figs. 4, E, and 5, E) can be taken as representing the nor-
mal pattern of endocardial activation of the right ventricle.

The tracings obtained from cases of right bundle l)ranch Ijloek diffei’ es-
sentially from those discussed before. Eight bundle branch block records di.s-
played prominent positivity during most phases of ventricular activation (Figs.
2, 3, and 4). This is to be expected if one assumes that in instances of right
bundle branch block the septum and the right venti’icular cavities are being ac-
tivated from the left ventricle, and that therefore a layer of jmsitive charges
faces the right ventricular eaA'ity during the major part of vcntriculai’ excita-
tion. The occasional biphasie QKS complexes which were observed have their
analogue in animal c.xperiments. Thi.s, it .seems, indieate.s a radial spread of the
action current over the endocardial surface after the impulse has reached the
right ventricular cavity through the intraventricular .septum and before it as-
sumes and comj)letc.s its course through the latei’al ventricular walls.

IIECHT: POTENTIAL VARIATIONS OP RIGHT HEART IN AIAN , 49

In the face of overivlielmiiig evidence in support of thg new nomenclature
of bundle branch block, it need hardl}'^ lie mentioned that ca\dty potentials of the
type recorded in man in intraventricular block could be obtained only if, in
records of the first type (Figs. 4, D, E, and E, and 5), activation is normal in
the right and delayed in the left ventricle (left bimdle branch block) ; and if,
in records of the latter type, it is delaj’^ed in the right but presumably normal
in the left (right bundle branch block) (Figs. 2, 3, A, and 4, A, 5,* and C).
The human records which have been presented are in accord with records of
certain pertinent animal exiieriments which have been based on the assumptions
that the action currents of the heart muscle may be represented as electrical
doublets, or as an electrical source followed immediately by an electrical sink,
that they follow the laws which govern the flow of electrical currents in volume
conductors, and that the pathways which the action current traverses are identi-
cal to those worked out over many jmars for various species of mammalian and
nonmammalian hearts.

The Meanh\{j of Vjt . — It remains to explain the more complex ventricular
records which are obtained when the exploring electrode is situated at upper
auricular levels. It has been pointed out that the ventricular complexes recorded
from this region are quite similar to, and sometimes identical with the so-called
unipolar leads from the right arm. They differ from tracings obtained from
lower auricular or ventricular levels in eases of right or left bundle branch
block but are similar to records from lower auricular levels in nomally activated
hearts. It has been stated that the right arm potentials (Yr) represent po-
tential variations of the ventricular cavities transmitted to this region by the
large vascular openings at the base of the heart.^^’ It now appears that cer-
tain modification of this statement can be made. The auricular deflections in
Yr are unlike the deflections in records made from the auricular endocardial
surface but are similar to the deflections obtained when the electrode is located
extracardially in one of the venae cavae (Fig. 1). The ventricular deflection in
Yr is similar to that of endocardial records from the upper, but not from the
lower auricular region. YTlien the electrode is placed in the upper auricular
position, the tip lies to the right and above both ventricular cavities and the
intraventricular septum (Fig. Q, B). This position favors the recording of a
mixture of potential variations from the basal parts of both cavities. In a nor-
mally activated heart, the potential variations of both cavities are negative, and
consequently a deflection of QRS directed chiefly downward will be recorded
regardless of whether the electrode records the potential variations of one or of
two ventricular cavities. In left bundle branch block, the potential variations
of the left ventricle are positive for the same reason that, in right bundle branch
block, those in the right ventricle are positive. An electrode placed above and
to the right of both ventricles ivill record a mixture of the positive potentials
of the left and the negative potentials of the right ventricular cavity. As the
right ventricle is closer to the exploring electrode, the effects of the right ven-
tricular cavity wall manifest themselves to a greater extent than those of the
left, and the major portion of the electrocardiogram will show^ negative deflec-
tions. Tliis preponderance of negativity will be particularly evident during the

50

AMERICAN HEART JOURNAL

later phase of activation, when the left ventricular cavity lil^ewise becomes neg-
atively charged as the impulse spreads through the lateral ventricular walls.
Under these conditions a mixed record of the type obtained in Fig. 4, E, re-
sults. In right bundle branch block, early negative deflections with final broad
R waves are tj'pical for a right arm lead (Vr) and have likewise been recorded
from upper right auricular levels (Figs. 2, 3, A, and 4, A and B). Again it
seems likely that primary negative left ventricular potentials are responsible for
the early part of QRS and that the large slurred R wmves of the later phase arc
a reflection of the positive QRS complexes of the right ventricular ca^ity. Fig. 6
illustrates diagrammatically the position of the exploiing electrode in relation to
the potential variations of both ventricular cavities.

A B

Figr. 6. — The relationship of the exploring' electrode to the auncul^ and \entncul.ii
c.avities. In position A the electrode is placed low in tlie right auricle. Position i? at a
higher auricular level and therefore permits the recording of the potential variations of botn
right and left ventricuiar cavities (see text). The circle in the right auricle indicates the
position of the inferior vena cava.

SUMMARY

1. Electrocai’diograins from the endocardial surfaces of the right side of
the heart and from the large veins have been obtained by means of a catheter-
like elccli’ode imseiled through the right or left antecubital veins.

2. The potential variations which have been recorded are in agreement
with the basic concepts of origin, siiread, and distribution of the action cun'cnt
of the heart upon which modern electrocardiographic interpretation is based.
The conelu-sions which have been drawni from animal experiments can .safely
be applied to human elect I•ocardiograJfll^^

nECHT : POTENTIAL A^ARIATIONS OP RIGHT HEART IN JiIAN

51

3, The potential variations recorded from unipolar light arm leads repre-
sent auricular deflections similar to those present in the large veins. The ven-
tricular deflection in Vr is a faithful reproduction of records obtained from the
endocardial surface of the upper portion of the right auricle. They represent a
mixture of potentials from the right and left ventricular cavities.

Miss Jeanette Leloude gave valuable assistance.

REFERENCES

1. Craib, \V. U. : The Electrocardiogram, Loudon, 3930 Medical Re.scarcli Council, Special

Report Series No. 347.

2. Wilson, F. N., Macleod, A. C4., and Barker, P. S. : The Distribution of tiie Currents of

Action and of In,iury Displayed by Heart Muscle and Other Excitable Tissues, Ann
Arbor, 1933, University of Michigan Press.

3. Macleod, A. G. : The Electrogram of Cardiac Muscle: an Analysis 'Wliich Explains the

Recession or T Deflection, Ast. Heart J. 15: 165, 1938.

4. Baylej', E. H. : The Potential Produced by Cardiac Muscle. A General and a Particular

Solution, Proc. Soc. Exper, Biol. & Med. 42: 699, 1939.

5. Harris, A. S.: The Spread of Excitation in Turtle, Dog, Cat and Monkey Ventricles,

Am. J. Physiol. 134: 319, 1941.

6. Lewis, Th.: Galvanometric Curves Yielded by Cardiac Beats Generated in Various

Area's of the Auricular Musculature. The Pacemaker of the Heart, Heart 2: 23,
1910.

7. Lewi.s, Th., and Rothschild, M. The Excitatory Process in the Dog’s Heart:

the Ventricles, Phil. Tr., Lond. Series B 207: 247, 1916.

S. Wilson, P. N., Hill, T. G. W., and Johnston, F. D.: Tlie Interpretation of Galvano-
metric Curves Obtained "(vhen One Electrode Is Distant Prom the Heart and the
Other Near or in Contact With the Ventricular Surfaces. II. Observations on the
Mammalian Heart, Alt. HUtVRT J. 10: 163, 1934.

9. .Tohnston, F. D., Hill, I. G. W., and Wilson, P. N. : The Form of the Electrocardiogram
in Experimental M 3 ’’ocardiaI Infarction. II, The Early Efi’ects Produced by
Ligation of the Anterior Descending Branch of the Left Conmary Artery, Am. Heart
J. 10: 889, 1935.

30. Rosenbaum, P. P., Erlanger, H. Cotrim, N., Johnston, P. D., and Wilson, P. N. : The

Effects of ^interior Infarction Complicated by Bundle Branch Block Upon the Form
of the QRS Complex of the Canine Electrocardiogram, Am. Heart J. 27: 783, 1944.

31. Johnston, F. D., Wilson, P. N., and Hecht, H.: The Precordial Electrocardiogram in

Mjmeardial Infarction Comiilicated by Bundle Branch Block, J. Clin. Investigation
18: 476 3939.

32. Wilson,* P. N., Johnston, P. D,, Rosenbaum, P. P., Erlanger, H., Kossmann, C. E.,

Hecht, H., Cotrim, N., Menezes de Oliveira, R., Scarsi, R., and Barker, P. S.: The
Procordial Electrocardiogram, Am. Heart J. 27: 19, 1944.

33. Ivo.ssmann, C. E., and .Tohnston, P. D.: The Precordial Electrocardiogram. I. Potential

Variations of the Precordium and of the Extremities in Normal Subjects, Am.

Heart J. 10: 925, 3935.

14. Wilson, P. N., .Tohnston, I'"'. D., Cotrim, N., and Rosenbaum, P. P.; Relations Between
tho Potential Vuiaations of the Ventricular Surfaces and the Form of the Ventricular
Electrocardiogram in Leads Prom the Precordium and tho Extremities, Tr. A. Am.

Physicians 56: 258, 3941.

15. Helm, j, D. Helm, G. H., and Wolferth, C. C.: The Distribution of Potentials of

Ventricular Origin Below the Diaphragm and in the Esophagus, Am. Heart J. 27:

755, 1944. r.

16. Cournand, A., and Ranges, H. A.: Catheterization of Right Auricle in Man, Proc. Soc.

Exper. Biol. & Med. 46: 462, 3941. ......

37. Macleod, A. G., and Cohn. A. E.: A New Piezoelectric Manometer to Record Intra-
cardiac Pressures and for the Simultaneous Recording of Intracardiac Electro-
grams, Am. Heart J. 21: 345, 1941.

18. Bozler, E.: The Initiation of Impulses in Cardiac Muscle, Am. J. Physiol. 138: 273,

1943.

19. Bayley, R. H.; Theoretical Genesis of Q as Observed in the First Three Standard

ijeads of the Electrocardiogram: a Preliminary Report, ,T. Trop. Med. 41: 144,

1938.

20. Gardberg, M., and Ashman, R.:
Med. 72: 210, 1943.

The QRS Complex of the Electrocardiogram, Arch. Int.

CLINICAL PICTUEE AND TREATMENT OE^ THE LATER
STAGE OP TRENCH FOOT

JIajor David I. Abramsok, M.C., Captain David Lerner, M.C.,
Lieutenant Colonel Harris B. Shujiacicer, Jr., M.C., ^vnd
Lieutenant Colonel Ford K. Hiok, ]\I.C.

Arjiy op the United States

introduction

D uring world War I, the single winter campaign in which the Ground
Forces of the United States were involved resulted in approximately
2,000 cases of trench foot. In World War II, casualties of this type have been
eonsiderablj- greater due to the fact that a far larger Ai*my took part in a
number of winter campaigns.

A large proportion of the soldiers with trench foot have alread.v returned
to civil life, while those still in the Army vdll also be leaving in the near future
as demobilization takes place. As a result, the burden of continuing the treat-
ment of the sequelae of this condition will fall upon the general practitioner
in civil practice as well as the physician in the Veterans’ Facilities. It is, there-
fore, the purpose of this paper first to present the clinical picture of the patient
with trench foot approximately eight months after the initial exposure and,
second, to discuss the results of the various procedures that have been at-
tempted in the later tinatment of this condition. In order to evaluate the
sequelae, it will be necessary, for comparison, to describe binefly the initial stages
also. For the .sake of simplicity in presentation, all the cases liave been
arbitrarily grouped into Lvo categories, namely those Avithout any significant loss
of tissue, and those with deep gangrene.

Distxnciion Between Trench Foot and Other Conditions Besutiing Irom
Exposure to Cold. — Trench foot develops in soldiers compelled to remain in
foxholes or trenches for a prolonged period of lime during which their feet are
exposed to a damp environment and to cold not nece.s.sarily low enough to freeze
tissues. Tlie almost continuous contact of the skin Avith Avater adds to the hazard
of thermal injuiy, since as a result there is a facilitated transmission of cold
to the tissues as aa'cII as an increased rate of loss of body heat. A further factor
faAmring ti.s.sue damage is the reduction of the circulation due to the general
muscular inactivity and the cramped position in AAiiich the loAver extremities
tlirough necessity mu.st remain for I'clatively long inteiwals. Immereion foot
develops in survivoi's of shipAvreeks comi)elled to keep theii' feet constantly or
intennittently immeiscd in cold sea AA-ater for periods of days or Avccks AA'hile

rn-’tent^'d In part brforc the Llghtcf'nth Annual irectinc of the Control Soclcp' for Cllnl-
t xl Jt< search. Chicoffo. Nov. 2. ond before tho Mctlical Conference of tlie Sixth Service

Coninrind. f. S. A.. ChlcoKO, Nov. D, 1PJ5.

neex-hfU for publlcotlon D‘ c. 12. 1945.

, ABKAMSON ET AL. : TBENCH FOOT

53

on rubber rafts or in boats. Again, the environmental temperature often ranges
around 33° F. Actually, very little dijfference exists between this state and trench
foot.

In eontrast, common frostbite and high altitude frostbite follow actual
freezing of tissues by exposure to sub-zero weather. High altitude frostbite
develops in members of aiiplane crews at high altitudes, when exposure takes
place either through some failure in the heating unit of the suit, or on even
momentary withdrawal of an extremitj'" from a heated glove or boot. In neither
this condition nor in common frostbite does the factor of exposure to water oi‘
mud play an important role.

CLINICAL OBSERVATIONS

The data in the present report were obtained from a study of 633 patients
(616 enlisted men and 17 officers) ivitli varying degrees of trench foot, who came
under observation two to tliirteen months after exposure to the elements. Tliese
men remained under our care for from two to seven months and were then eitlier
returned to duty or discharged from the Army.

Patients With One or 3Iore Exposures and No Gangrene . — Of the entire
sei’ies of 633 patients, 596 or 91.2 per cent had one or more distinct exposures
without having developed deep gangrene on any occasion. Of this gi’oup, 526
had onl 3 ’' one attack wliich was sustained in combat either in Italy in the period
from November, 1943, to March, 1944, or in France, Germany, Luxembourg,
Holland, or Belgium, between October, 1944, and January, 1945. The duration
of exposure varied between three and fifty-four days, witli an average of four-
teen days. In practically all instances, the environmental temperature was
around freezing or slightly above that point, and the patients were exposed to
almost continuous rain. For the most part, their feet were immersed in water
and mud for a number of days, without the opportunit}^ of changing socks and
shoes, except at rare intervals.

Seventj'' patients had had two or more attaclvs without developing deep
gangrene. Sixty of them were exposed to the elements on two, and 10 of them
on three distinct occasions. In the later instances, the.v sustained either a fresh
case of trench foot or an exacerbation of the initial one. In the ease of tlic
patients with two attacks, tlie first exposure was in Italy from November, 1943,
to March, 1944. The duration of the exposure was about the same as in the case
of the gi’oup with a single attack, namely, an average of fifteen days, witli a
range of from one to sixty days. All of these patients were hospitalized for an
average of nine weeks and then sent to convalescent camps or reconditioning
centers, from which they were eventually assigned to duty. The second ex-
posure in this group took place in the period between August, 1944, and Febru-
ary, 1945, in France, Gennany, or Holland. Again these soldiers were hos-
pitalized, but this time they remained as patients until they reached this hospital.

The 10 individuals with three exposures experienced two of these in ItaB*,
first at Cassino and then at Anzio, and the third in Prance, Germany, or Holland.
Following each of the fii’st two attacks, the patients were returned to duty after

54

a:\ierican heart journal

a varying period of hospitalization. With the third exposure, they were hos-
pitalized for the last time, reaching this hospital approximately two months
after the acute stage.

Patients With Deep Gmgrene and Sn-hsequent Loss of Tissue . — Only 37
patients (5.8 per cent) sustained deep gangrene of the feet wdth the resulting
loss of tissue. This occurred after one exposure either in Italy in the period
between November, 1943, and March, 1944, or in France, Germany, Belgium, or
Luxembourg, between October, 1944, and January, 1945. The average period
of exposure was eight daj^s, vdth a range of from one to thirtj^-four days. All
of the patients in this group were at complete bed rest when they reached this
hospital approximately two to six months after the initial injury.

It is of interest to rrote that irr both patierrts with arrd those without deep
gangrene rro correlation exists betrveen the severity of the corrdition and tlie
dnration of exposru'e to the elements (Table I). Furthermore, it worrld appear
that the individuals with an old liistory of frostbite or a previous attack of trench
foot are no more liable to develop gangrene than are those exposed onlj^ once.

Table I. Pkequbncy of Loss of Tissue in Series of G33 Patients and Correlation With

Other Factors

extent of pathology

NUMBER

OP

OASES

%

ENTIRE

SERIES

AVERAGE
PERIOD OF
EXPOSURE
(DAYS)

THOSE WITH
PREVIOUS
EXPOSURES
(% OF
GROUP)

THOSE WITH
OLD HISTORY
OF FROSTBITE
(%OP
GROUP)

Complete los-s of one or both feet

1

0.1

12

0

0

Loss of toes and part of foot,

2

0.3

7

0

0

both sides

Loss of toes and part of foot, one

1

0.1

4

0

0

side

Entire loss of one or more toes,

3

0.5

0

0

0

both feet

Entire loss of one or more toes,
one foot

7

1.1

12

0

0

Loss of part of one or more toes

23

3.0

7

0

10

or heel

Superficial gangrene, more exten-

33

O.rj

<)

0

0

Bive

Superficial gangrene, mild

15

2.4

0

0

0

No loss of tissue

548

SO.fi

14

12.8

7.7

Clinical Picture Shortly After Exposure . — Tlie first .s^nnptoms experienced
by most of the patients in the series were not severe or violent pains, Inrt rather
numbness, an aching sen.sation, intense coldness, and swelling of the feet. In
some instances, the soldiers were compelled to seek medical aid after they bad
removed their shoes and then were unable to replace them because of the swell-
ing. On leaAung the fo.xliole and beginning to walk, a number of men ex-
perienced severe pins-and-needlos sensations on the plantar surface of the feet.

By the time the soldier's reached a fi.xod installation, it could generally be
determined whether or not they were going to lose any significant quantity of
ti.ssuc. In tho.se individuals who were fortunate enough to escape without any
gangrene or perhaps with only involvement of the superficial layers of the .skin,
the feet were found to be cold, ])ale or cyanotic, swollen, and painful. In the

ABRAMSON’ ET AL. : TRENCH FOOT

55

severe caBCs, swelling and discoloration were marked. In man7 of tliese, vesicles
were present on the dorsum of the feet, which, in some instances, developed into
large painful blisters containing lemon-colored or clear serous fluid. In most
individuals desquaination of practically the whole sole was present, and in some
this occurred a number of times. FoUomng the loss of dead epidermis, the feet
began to perspire. This generally occurred while the patients were still at bed
rest, and, although minimal at the beginning, it became marked in many in-
stances. Sweating was most often noted in the foot that was cold and cyanotic,
but it was also present when the extremity was Avarm and of normal color.

As the patients remained in the hospital, onl}^ a small number of them
demonstrated a transient period of hyperemia, as manifested by marked Avarmth
and' redness of the sldn of the foot. This response subsequently disappeared
and the foot became tAq)ically cold and cyanotic. The cyanosis Avas generally
accentuated b.y dependency. Frequently the patients suffered from severe,
burning pain, particularty at night, from AA^hich they sought relief b}’’ uncover-
ing their feet.

For the most part the patients AAuth deep gangi’ene demonstrated the same
early signs and S3Tnptoms except that the clinical picture Avas of a more severe
nature. .Marked sAvelling, qA’anosis or pallor, blister formation, severe pain in
the feet, and numl^ness Avere common findings. In some instances gangrene
Avas already present when the patient reached the Battalion Aid Station, but
more often it appeared onty after six to ten days of hospitalization. At times
the gangrene aa^s preceded b.A' large hemorrhagic blisters. The involved areas
quickly became black and mummified. In some indiAuduals ulcerated sites Avere
present; above these the tissues shoA\’'ed signs of inflammation. In others com-
plicating infection alreadj^ existed.

It is not AAdthin the scope of this paper to discu-ss treatment during the
early stage of trench foot. From a rcAUCAv of the records of the patients studied,
it is difficult to assay Avith any degree of accuracy the relatiA^e Avorth of the
various measures AAliich had been initiated.

SEQUELAE

Manifestations of the later stage of trench foot, as studied in this hospital,
can grossly be divided into three general categories. One group of patients
demonstrated signs .suggestive of excessive sjunpathetze activity, but had minimal
complaints. Another group had symptoms referable to inAmlvement of peripheral
ncz.‘ves, but ,.shOA\"ed fcAA^ objective findings. The patients in the third group dis-
])layed both subjectiAm and objectiA'^e clinical manifestations.

. Patients WUh Predominant Signs of Excessive Sympathetic Activity.— Oi
the entire group of izatiezits, 144 (22.8 per cent) demonstrated findings AAffiicli
AA’^ere primarity the result of excessive sympathetic activity. The skin tempera-
ture of the toes Avas found to be Ioav; frequently loAAm- than the eiiAuronmental
temperature. Hyperhidrosis also Avas present, Aurying from slightly gi’eater
than normal to the point where the .sAveat lulled off the foot almost in a con-
tinuous floAV. The quantity of perspiration Avas definitely increased by emotional

56

AMERICAN HEART JOURNAL

factors. The fact that the skin temperature was lower than the environmental
temperature was due to the cooling effect produced by the evaporation of per-
spiration. Cyanosis of the feet, particularly in the dependent position, was
also a prominent finding in this group.

A number of patients would occasionally show a change from a blue, cold
foot to a red, hot one. This effect could be produced by exposing the extremities
to a warm room or, in some instances, by wmlking a short distance with shoes on.
At other times, for no apparent reason, the foot would become red and hot, and
then revert to a cold state. Mottling of the skin was a fairly common finding.
In some patients this was only a transient phenomenon, ■while in others it re-
mained for a relatively long period of time. Various types of patterns were
present, occasionally in the same individual. For the most part the mottling
was produced by sharply demarcated areas of rubor on a background of cyanosis,
intei-spersed with patches of pallor.

Examination of the large peripheral vessels in the patients Avith no deep
gangrene revealed the absence of the dorsalis pedis artery, either on one side
or both, in about 6 per cent of cases (Table II) . Wliether or not this finding
had anj^ significance is difficult to state since comparable results have been noted
in groups of normal soldiers. No signs of arteriosclerosis Avere observed in
any of the patients in the series. In the case of the individuals AAuth deep
gangrene, the dorsalis pedis artery aa'Us not palpable in those instances in AA'hich
the process had extended onto the dorsum of the foot. Similarly, in one in-
.stance, the posterior tibial artery could not be felt, A history of intermittent
claudication Avas obtained only infrequently, thus suggesting that for the most
part there Aims no impairment of the blood supply to the muscles of the legs.

Tahi.k II. ;m.\nikkstatioxs Four to Tuirteen Months AtWER Exposure in a Series ok 590

P.ATIENTS AViTHOUT GANGRENE

FREQUENCY

frequency

SI(iX.S

%

SYMPTO.MS

%

Cyanosis

59.1

Aidiing

3.8

Atispnt pulsations, large

6.0

Tenderness in sole of foot

1.3.6

arteries

Sweating

50.4

Numbness

16.6

•Abnormal giiit

34.0

Neuritic pains

14.3

-Vtropliv of musele.c'

14.7

Hypestliesia

41.5

Stiffness of toes

10.0

Burning and tingling

21.9

Coldness

27.9

Edema

17.4

Oscillomefric readings Avero performed on the fii’st 40 patients examined,
and no significant alterations Averc obseiwcd. The effect of indirect vasodilata-
tion, brought about by applying hot-AA'aler bags to the abdomen and che.st and
covering the .sub.iect Avith a number of AA’oolen blankets, aatis studied on 25 sub-
jects. Tn all instances, this piMcedure brought the skin temperature, AA'hich AA'as
loAA* at the beginning, to a level considered to be normal under the.se circum-
stances. In 11 cases, a paravertebral lumbar sj'inpathetic block Avith procaine
AA'a.s done and a similar type of skin temperature respon.se A\-as obtained. IVith

ABRAMSON ET AL. : TRENCH FOOT 57

the rise in the skin temperature, the e^mnosis of the foot was replaced by rubor
and the hyperhidrosis disappeared entirely for a. short period.

In 10 patients with cyanosis but no deep gangrene, the reactive hyperemia
test^ was performed. In all individuals the hush, which appeared on removal
of the pressure in the euif, spread over the leg within five seconds and involved
the toes maximally in ten seconds. The flush faded out in about one to two
minutes. The rapidity of the response indicated a normal reaction of the cu-
taneous arterioles and small vessels (capillaries and subpapillary venous plex-
uses) to a period of anoxia and helped to rule out the presence of occlusive
vascular disease in these vessels.

The above tests substantiated the view that the late findings in this group
were due primarily to excessive sj^mpathetic activity rather than to organic
involvement of the blood vessels of the lower extremities.

Patients With. Manifestations Referable to Peripheral Nerve Involvement . —
The second categor}'- included 63 patients (9.9 per cent) in whom the signs and
sjTnptoms were suggestive primarily of some type of peripheral nerve involve-
ment. Objectiveh'" there were frequently veiy few abnomalities noted. The
main complaint was tenderness over the metatarsophalangeal portion of the
foot, which at times was of such a degree that the patients did not allow even
the slightest pressure to this part. As a result, some of them were luiable to
waUc at all, or, when they did, they placed their weight on the heel or along the
lateral edge of the foot. Manj'- of these individuals were found to have areas
of hypesthesia to pinprick and cotton wool, which corresponded closely to the
sites which were sensitive to deep pressure. The hypesthesia sometimes involved
the plantar and even dorsal surfaces of the toes and the dorsum of the foot.
Anesthesia was rarely present. In some individuals hyperesthesia was a dis-
turbing symptom. Sensation in the legs was only infrequently altered.

The patients in this group also complained of various types of paresthesias,
such as burning and stinging sensation and a pins-and-needles sensation in tlie
toek Furtheimore, they described shooting pains in the feet, which appeared
while at rest, and a sensation of numbness in some of the toes.

Patients With Both Synd,romes.—The third and largest group consisted
of 426 eases (67.3 per cent) showing signs and symptoms of both excessive
sympathetic activity and some tj^e of peripheral nerve involvement. Besides
these findings, many of the patients in tliis categor}’^, as well as in the other
two, entered the hospital still showing the presence of con.siderable desquamat-
ing, thick epidermis on the plantar .surfaces of the feet (Fig. 1). This material
gradually fell off, leaving new, thin skin. IMarked swelling .of the toes and,
to a less extent, of the feet was present in 28 patients (Fig. 2).

The presence of atrophy of the small muscles of the foot, giving the ap-
pearance of an abnoimally high arch, was observed to some degree in most of
the individuals and was quite marked in 26 patients. It was difficult to de-
termine whether the response was a nonspecific effect due to disuse or whether
it was pai’t of the pathology of the trench foot syndrome. However, the existence
of histologic alterations in the muscles and nerves in the initial phase of this con-

58

AMERICAN HEART JOURNAL

Pig. 1. — Typical case of hypei-keratosis of the skin three months after exposure to snow
and cold, wet weather for three days. Skin wrinkled and fissured, similar to type of rospon.se
.seen after long immersion of tissues in water. Dry gangrene at tips of toes. Normal pulsa-
tions in peripheral arteries.

Pig. 2. — i’eraistent swelling of feet and pro.sence of gangrene four months after e.vposure
to the eienu-nt.s for eight day.**. Granulating wounds of both great toe.s present and also .«oinc
infection.

59

ABRAJISON ET AL. : TREjN'CH FOOT

ditioii favois the latter view. In some instances, in spite of an intensive and
piolonged piograni of exei’cises utilizing the small muscles of the foot, these pa-
tients showed no beneficial effects and, at the time of discharge from the hospi-
tal, considerable atrophy still existed.

Osteoporosis of the bones of the feet was a fairlj* common finding in the
more severe cases. This may also have been either a response to the long
period of inactivity or part of the trench foot s 3 mdrome. In several instances,
the process was no longer present at the end of the period of hospitalization.
I\Iore frequently, however, very little change was observed in the final film after
two to three nionths of pln^sieal actimty. Whetlier or not this change is or-
dinarily’’ an irreversible one can only’^ be determined by’’ follow-up studies on
such a group.

Among the patients with one or more exposures and no deep gangrene,
there were 48 who entered this hospital still showing areas of superficial gan-
grene. These were generally’’ present on pressure points m contact vdth the
shoe, such as the medial a.spects of the feet (Fig. 3, A), the tips of the toes, and
occasionally^ the heels. For the most i^art, the gangrenous material separated
spontaneously’, leaving exposed a thin, tightly’ drawn, .smooth, shin.v skin which
gradually resumed a normal appearance (Fig. 3, A). It is of interest that in a
number of these patients the original description of the lesions would have sup-
ported the belief that a much more severe ty’^pe of involvement existed than
was substantiated by’’ subsequent events. Such findings are in accord ^vith the
view that ednservatisin should be practiced in the earl.v treatment of gangrene
of the feet in trench foot.

Practically’’ none of the patients showed vesicles at this stag’e of the disease.
Frequently’’ one or more toenails had fallen off, leaving the nail bed exposed ; or
the nails "were distorted with a considerable amount of debris beneath them.
Dermatophytosis was a common finding in this gToup.

Forty-two of the patients demonstrated marked stiffne.ss of the toes vdth
a shiny, firmly’’ attached skin. In some individuals, the great toe was widely’
separated from the others (Fig. 4) and was either h.vperextended (in the form
of a pseudo Babinski sign) or fiexed. These observations have been previously
described by’ other investigators.''’ There was no correlation between the de-
gree of stiffness and the severity’ of the condition originally’, and it was fell
that this response was iDrobably’ due in great part to disuse.

With regard to the group of 37 patients with deep and extensive gangrene,
frequently the gangrenous portions were partially’ separated at the line of
demarcation at the time of admission to the hospital. The lesion was generally
bathed in foul-smelling pus and in some instances there was evidence of extensive
infection throughout the gangrenous portions. On numerous occasions, where
the gangrene appeared to be of a dry’ ty’pe, removal of this material through
the line of demarcation disclosed a pool of pus beneath it.

Infection was invariably’ a mixed one and very commonly penicillin- and
sulfonamide-resistant Bacillus proteus and Bwillus pyooyaneus were present.
There was little spread of the. infection to the adjacent soft tissues, but osteo-
myelitis Avas frequently noted in the proximal stump.

ABRAMSON ET AL. : TRENCH FOOT

61

LATER THERAPY

j\Iost of t]ie patients with trench foot arriving at this hospital had been at
complete bed rest witlioiit latrine privileges for from one to twenty weelcs,
with an average of nine weeks. Therefore, the treatment, whenever possible,
was directed at making them ambulatory as rapidly as their condition permitted.
The problem of reconditioning was made more difficult by the fact that many of
the men still had considerable tenderness of the soles of the feet, pain, and swell-
ing. All these factors made the resumption of walking an unpleasant experience.
Therapy, therefore, was divided into two periods, namely, the medical and sur-
gical treatment, followed by the reconditioning program.

JIEDICAL AND SURGICAL TREATJMENT

Massaeje and Bemoval of Dead Epidermis . — Most of the patients showed the
presence of a considerable amount of desquamating epidermis (Fig. 1), Avhich
was removed by nibbing lanolin ointment, containing 4 per cent salicylic acid,
into the skin. The procedure was perfonned by the patient at frequent and
scheduled intervals during the daj^ under the supervision of a phy.sieal therapist.
When desquamation was completed, the ointment was replaced by mineral oil
and a dilute solution of alcohol for the purpose of massage. This step was car-
ried out at least twice daily for half-hour intervals either by the patient himself
or by the patient in the next bed. Considerable emphasis was also placed on
the practice of active manipulation of the toes in order to counteract the stiff-
ness, contractures, and atrophy of disuse. In some instances where these findings
were quite marked, the daily routine of massage was supplemented by passive
and active exercise of the toes by the physical therapist.

Typhoid Vaccine . — When jiatients with trench foot were first received at
this hospital, an attempt was made to determine the effect of typhoid vaccine
on the condition, A number of subjects picked at I’andom were given this
treatment; after a series of 10 to 15 intravenous injections every other day,
the results were analyzed. Preliminary testings were done on each patient and
the dosage of the vaccine was increased to the point where a single injection was
followed by a rise in body temperature to approximately 102° F.

For the mo.st part, this treatment brought about no definite change in the
clinical picture, except for a significant reduction in the swelling of the feet
in some instances. Typhoid vaccine was, therefore, subsequent!}’ utilized only
in those patients in whom edema was the main complaint. In 10 of 16 indi-
viduals, there Avas a rapid subsidence of the swelling after the finst or second
administration, and the therapeutic effect continued but was less marked with
the following 10 to 12 injections. At the end of the period, all of these patients
Avere fully ambulator}^, Avhereas previously they had been compelled to lie in
bed a considerable portion of the day because of the sAvelling. It is of interest
that complete bed, rest for a number of AA^eeks before this treatment had been
started had produced little change in the edema. In the remaining six patients,
typhoid vaccine did not have any therapeutic effect.

G2

AMERICAN HEART JOURNAL

It would appear, therefore, that this treatment has some promise and that it
should at least he tried in the ease of every patient vuth treneli foot who has
appreciable swelling of the feet. Whether or not it vull imve any effect can
be readily determined after the second or third injection.

Ortlioindic Appliances . — As soon as the patient without gangrene was
physically able, he got out of bed and began to wmlk, using low shoes. It was
felt that these would bo more satisfactory than the gai'rison shoes because of
their light w'eight and because less of the foot w^as covered, thus permitting
greater evaporation of perspiration. In patients in whom hyperhidrosis was
a prominent symptom, the shoes wmi'e perforated in a number of sites, to facili-
tate removal of the excessive perspiration by air currents.

Kipr, .S. — Applicjition of anterior heel in front of normal heel, to remove pressure from sole of

foot.

At least 182 of the patients witliout gangrene complained of tenderness over
the di.stal portion of the foot on the plantar siu’face. In an attempt to protect
this area from the weight of the body, these individuals, on walking, shifted the
pressure to the heel or to the lateral edge of the fool. In order to comiteraet
these unnatural gaits, with their resulting undesirable alterations in the dy-
namics of the foot and spine, a nibber lieel or a thick ])ieee of leather was at-
tached to the under siufface of the .slioe in front of the ordinary heel®' (Fig. b).
The patient then walked on the two heels, thus applying practically no pre.s-
.sure to the sole of tlie shoe which covered the .sensitive portion of the foot.
he continued to walk, the anterior heel which i-eceived most of the fiiction

nutliorf! arc- Indolitc’d to C.-iptain R. Ruck at tvlione cUKgcstion tills procedure was
piven a cllnlKil trial.

ABRAMSON’’ ET AL. : TRENCH FOOT

63

gradually wore doMoi, until eventually the pressure was again applied to the sole
of the shoe. In most instances, the sensitivity of the foot to pressure was lost
or diminished Ijy this time and the heel was removed.

Wormalin hy Tontophorcsis . — Since hyperhidrosis was a common and, at
times, incapacitating complaint, attempts Avere made to treat it, generally with-
out too much success. Low shoes, daily foot baths, foot poAvders, and frequent
changes of socks only partially counteracted this condition.

. At the suggestion of Preis,^ patients Avith severe hyperhidrosis Avere treated
AAnth formalin by iontophoresis. The use of formalin baths for hyperhidrosis
has been a fairly common therapeutic procedure in the field of dermatology
and it Avas felt that this action could be accentuated by forcing the fonnalin into
the skin by means of a gah'^anic current. A description of the procedure Ave
used to accomplish this folloAvs.

An ordinary galvanic current macliine Avas connected to the patient by
placing a large negatiAm electrode in close contact AAuth the abdomen, while the
positiAm electrode AAms immersed in a bakelite container filled with 1 per cent
formalin. The patient placed botli feet in the basin, AA’hieh Avas filled AAdth suf-
ficient solution to reach almve the ankles. Ten to 12 milliamperes of current
Avere applied for tAventy minutes. A series of treatments consisted of six daily
administrations.

In all instances the patients Avere fii’st skin tested for formalin sensitivity.
No patient AA’ho shoAved even the slightest reaction was grten this treatment.
The presence of sensitiAuty to formalin appeal’s to be fairly common, as indicated
by the finding that approximately 28 per cent of all the individuals tested shoAA'’ed
a positive reaction.

Results with formalin by iontoplioresis Avere rather variable. The therapy
was begun on 121 patients, but in 29 instances it had to be discontinued after
the second or third treatment because of the. appearance of a mild dermatitis or
fissuring of the .skin bctAveen the toes. Of the remaining 92 patients, 74 fini.shed
one series of .six treatments, Avhile 18 Avere given tAAm series, AAdth an average of
tliirty-nine days betAA’een treatments. In the case of the patients given one
series of treatments, 37 shoAved an almost immediate cessation of sAveating, 21
had a fair response, and 16 demonstrated no benefits from the therapy. The
patients AA’erc re-examined at the end of a four-Aveek period, and, at that time,
it wa.s felt that in seven the therapeutic effect was excellent, in 32, good, in 16,
fair, and in 19, poor.

Eighteen patients AA’cre giA’cn a second series of treatments either because
no therapeutic effect AA’as noted initially or because the reduction or cessation
in sAA’eating Avas onty temporary. In this group, the second series produced a
good result in six, a fair response in eight, and a poor result in four patients.

. All of the patients discussed Avere seen at intervals during the subsequent
tAvo months, and it Avas noted that in the great majority of them hyperhidrosis
Avas returning, iDut generally not to the same degree as previously. The therapy
evidently has a definite but transient effect on reducing SAveating of the feet in
trench foot.

64

AMERTCAX HEART JOURNAL

Luvihar Sympathectomy (Table III). — Since vasoconstriction is one of the
fundamental factore in the pathogenesis of trench foot and also one of the most
constant sequelae, the use of sxmipathectomy as a possible therapeutic aid has
been proposed and has received some clinical trial. This procedure -was there-
fore utilized in a number of individuals in this series."' In nine patients the op-
eration was done primarily for cold sensitivity or excessive hyperhidrosis, vith
the result that the feet became warm, dry, and normal m color. In two instances
in which maceration of the skui and infection had been present, these finclings
cleared up shortly after sympathectomy. In all nine patients the abnormal re-
sponse to cold and the associated discomfort were also minimized.

In 10 indirdduals in whom sympathectomy was performed primarily be-
cause of irain on rveight liearing, the results were variable. Two patients with
pain both in the metatarsal region and in the heels experienced complete relief
in the latter site only, while those with symptoms in the metatarsal region alone
were for the most part not benefited by the procedure. Somervliat similar re-
sults have been reirorted by Edwards, Shapiro, and Ruffin.® Sympathectomy
was also used in a group of patients with deep gangrene, and the results in this
type of case will be discussed in the section following.

A. n.

Fig. G. — A, Dei!|) gangrene of toes of boll, feet two month'- .iftd expo'-tire to snow -''tYl
cold, wet ANUither for six dass. Aiea« of dr> gangrene dcniircited ftoin noimil ti«‘'UC I-oiil-
Miiclllng discharge prc'ient from these «ites’ Normal o-cillometric rc.idings and normal pul-
sations m large aiteries of feet. B, Complete healing two montli- latci. following fc>ini'.i-
thectomy. amputation of gangrenous toes and. subsequontl.\ , pedicle tian>-fcr gr.ifts.

Trutimini i>f Exircmilicf, With Dap Gangmu . — In only one of tlic pa-
tients with deep gancrene had any surgical procedure been performed befoio
admission to our hospital. In all others, steps had to be carried out to remove
the gangmious material (Fisr. 6). In order to facilitate healiini, sympathectomy
was performed us a preliminary step in 30 patients; in eight of these, the pro-
cedure was done bilaterally (Fig. 6). Frequently, removal of gangrenous ma-
terial and portions of toe.s was carried out at the saim* time. Twenty-nine

♦A th til lied wn tlj iti” (..f tic cnirno and limit.ilionv of -i\ mp.itic clomi hi-, Icfn fportid
in ft pn’-nti- piici.f

ABRAMSON ET AL. ; TRENCH FOOT

65

Table III. Indications for Use op Lumbar Sympathectomy

CONDITION

RESULTS

Hyperhidrosis alone

Complete cessation of
sweating

REMARKS

Hyperhidrosis ivitli maceration
of skin and secondary infec-
tion

Marked cyanosis and coldness
and abnormal response to
low emdronraental tempera-
ture

Tenderness of sole of foot on
walking

Neuritic manifestations

Deep gangrene requiring ampu-
tation and skin gi-aft

Complete cessation of
sweating wntli healing of
skin

Return of normal color
and skin temperature

Only oceasionallj' effective
Only occasionally effective
Aids in healing

Operation generally not in-
dicated for this state
alone

Operation definitely indi-
cated

Operation indicated in some
instances

Operation not performed
for this condition alone
Operation not performed
for this condition alone
Necessary preliminary step
in many cases

Fig. 7. — Marked gangrene involving entire foot bilaterally, one month after exposure to snow
and cold, wet weather for thirteen days. Both feet subsi’quently amputated.

amputation .s ^ye^e performed, and in each instance conservatism with regard
to the amount of tissue removed was practiced. Nine patients required split-
thicloiess .skin grafts. In two cases, in which ends of metatarsal bones were ex-
posed Muth large .skin defects, it was necessary to utilize pedicle transfer grafts
from the opposite lower extremity in order to obtain well-padded, full-thickness
skin (Fig. 6, JB). One patient with gangrene of both feet was sent to an ampu-
tation center for further treatment (Fig". 7).

^ When the patients became ambulatory again, they were fitted with special
shoes to help overcome the difficult 3 '' produced bj'^ loss of tissues of the foot.
In most individuals in this group, however, veiy little was required since a
useful foot remained.

With respect to the evaluation of sympatheetomj’’ in the treatment of gan-
grene, it must be pointed out that no control series of cases was run simul-
taneously. Hence, there is no unequivocal evidence that the rate of healing was
affected by the procedure. Nevertheless, there was some indication that the
inerea.se in; circulation which followed had a beneficial effect in those instances
in which marked vasospasm was present.

(iG

AMERICAN HEART JOURNAI,

With regard to the use of split-tliickness skin grafts and transfer pedicle
grafts, there is little question that these procedures definitely reduced tlie period
of invalidism. Furthermoi’e, as a result, a thick layer of skin which responded
well to the application of pressure and friction now covered the stump (Pig.
Q. B) instead of the usual thin, poorly nourished skin vdiieh would have followed
as a natural course.*

Therapcniic Procedures of Questionable Value . — A certain number of ther-
apeutic procedures were attempted with little hope that they would prove ef-
ficacious. As anticipated, the results wei'e for the most part unsatisfactory.
However, the data will be presented, so as to discourage further clinical trials
of these medications by other worker's.

Pour patients with marked signs of excessive sjanpathetic tonus were given
a serias of six daily treatments rvitli meeholyd (aeetyl-beta-methyl-choline chlo-
ride) by iontophoresis. The procedure rvas similar to that used in the case of
formalin by iontophoresis (discussed prertously), except that a 0.2 per cent
aqueous solution of meeholyl was utilized instead of formalin. It was felt that
since meeholyl by iontophoresis is a good local vasodilating agent," the pro-
cedure might help in counteracting the vasospasm which existed in the patients
in this group. In each instance the feet became wann for a short period follow-
ing the treatment, but then reverted to the previous cold, blue state. At the
end of the sei'ies of treatments, no pennanent effect on the condition of the blood
vessels was noted in any of the patients and the method was therefore discon-
tinued.

In 11 patients with predominantly peripheral nenm involvement, the effect
of large doses of thiamine chloride administered intravenously was studied.
Each patient was given 100 mg. of the drug daily for an average of two weeks.
No untoward effects were noted following the treatment, and similarly no altera-
tion in symptoms occurred. The patients continued to complain of paresthesias,
aching and burning, and sensitivity in the soles of the feet. No data Averc ob-
tained from the study Avhich AA'Ould suggest that this tAqje of therapy Avas at all
Avorth Avhilc in the treatment of the neuritic complaints present in the later
stage of trench foot.

The effect of Buerger’s exercises and Sanders’ bed AA'as studied in eight pa-
tients Avith moderately severe trench foot but no gangrene. No olndous altera-
tion AA'as noted in .such signs as cyanosis, coldness, or hyperhidrosis; nor aams there
any reduction in the severity of the .symptoms.

In 11 patients, paraA'ertebral lumbar sympathetic blocks Avere performed.
As mentioned previously, this Avas carried out to determine Avhether or not the
cyanosis, coldness, and hyiicrhidrosis Averc due to e.xccssiA'e sympathetic tone.
At the .same time, an opportunity Avas afforded to study the therapeutic effect
of such a jii-occdurc. In fn-e instanco.s, the symptoms Avere unchanged. Tlic
tcndernc.ss OA'cr the sole of the foot, the sAvelling. and the neuritic pains Avero
not affected. However, in the remaining six patients, some allcA’iation of the
.scnslfiAity of the .sole of the foot re.sulted, but this lasted for only a short jicriod

*.V nnnlyj'is of tljo .^urjrlral m.mngonif'nt of frariKronc In trench foot will he re-

jhirK-il in ti "opamte puiiUiViTlon.

ABKAMSON ET AL. ; TRENCH FOOT

67

of time. It is of interest that, when a number of these were subsequent!}' sym-
pathectomized, the therapeutic effect was much less than anticipated on the
basis of the findings following the block.

RECONDITIONING PROGRAM

A number of patients with trench foot did not immediately become ambu-
lator}’" on reaching the hospital either because of the presence of gangrene or
infection or because there was marked sensitivity of the soles of the feet which
did not permit weight bearing. A special type of reconditioning program was
therefore instituted to take care of these individuals during the period that they
were compelled to remain in bed in order to prepare them for the time when
the}’" could participate in more active physical exercise. The routine consisted
of morning corrective exercise in bed and afternoon sessions of games, tourna-
ments, and various types of physical fitness testing.

As soon as the patients were able to walk around the ward without too
much difficulty, they were started on an aml)ulator}^ reconditioning program
whicli for the first four v’eeks consisted of exercises requiring them to be on their,
feet only a small portion of the time. Dining the second four-week period, this
was gradually increased until the desired level of activity was reached. Then
it was maintained for varying periods of time ranging from another month to
three months, depending upon the rate of progress of the indiiidual patient.

The men were given various t}T)es of rather strenuous ealistlienics in a pool,
since it was felt that under these circumstances the buoyancy of the water would
permit more vigorous use of the muscles of the feet with less associated pain and
would also help in the reeoveiy of a sense of balance. Except for an occasional
individual who responded poorly to immersion of the feet in water, the men
participating in this part of the program appeared to benefit from the exercises.

At the same time, the patients were encouraged to ride a bicycle since tliis
sport helped to improve the tone and the strength of muscles of the lower ex-
tremities. Group walldng at a leisurely pace was also an important part of tlic
program. . The distance covered was gradually increased until it consisted of
from 1 to 2 miles. The main pui'pose was to accelerate the rate at whieli toughen-
ing of the skin on the soles of the feet was taldng place.

Results With Reconditioning Pror/mn.— The first therapeutic effect from
the reconditioning program was a rapid change in the mental outlook of the
trench foot patient. Having led a life which was very similar to that of a bed-
I'idden inva;lid for the previous two to three months, he suddenly found himself
part of a program of gradually increasing physical activity. He began to do
tilings which he did not believe he would ever be capable of perfonning again,
and gi'adually, as his general physical condition improved, his self-confidence
also returned. Constant participation in competitive sports helped change his
attitude toward future duties and responsibilities.

When it was felt that the patient with trench foot had obtained maximal
benefit from reconditioning with respect to his general health, and that his feet
were sufSeiently recovered to allow taldng part in a fairly normal program of
daily physical activity, hospitalization was terminated.

68

AMERICAN HEART JOURNAL

FINDINGS AT FINAL EXAMINATION

Except for 51 men who were transferred to convalescent centers or to otlier
liospitals, the patients were sent either to a limited t>T)e of duty or were dis-
charged to civilian life. The factors which were taken into consideration before
a decision was reached were the severity of the signs and s.tnnptoms that still
persisted, the rate of progress of the case in the hospital, the period of total
hospitalization, the mental outlook of the patient, and the presence of nmltijilc
defects. Among the signs and sjTuptoms, the ones that were given special at-
tention were; the tjqie of gait, the degree of hyperhidrosis, the presence of
atrophy of the small muscles of the feet, the actual loss of tissue as a result of
gangrene, the distance the patient was able to walk without difficulty, the
tendency toward blister formation and fissures, the state of the skin on the solos
of the feet, and such complaints as paresthesias and tenderness of the soles of
the feet.

Patients Pcturn^d to Duty . — In the case of the group returned to duty
(33 per cent of the series), most of the men were able to walk without difficulty
for at least a mile and they all had a normal gait, placing the pre.ssure properly
on the entire foot. They were also able to stand on the distal part of their feel
and elevate the heels from the gi’ound. There were no signs of excessive sweat-
ing, coldness, atrophy of the small muscles of the feet, or stiffness of the toes.
Cyanosis was minimal. There were very few complaints of pares! he.sias, numb-
ness of the toes, or tenderness of the soles of the feet on walking. These patient.s
had no other medical or surgical conditions, including any type of wound witii
- residuals. During their period of hospitalization, they had shown fairly rapid
progress.

Patients Discharged to Civilian Life . — In the case of the patients di.scharged
from the hospital to civilian life (67 per cent of the series), approximately one-
third had an associated condition or conditions wdiich by themselves might not
have been disabling, but together with a moderate degree of trench fool were
sufficient to necessitate discharge from the Army. These medical defects con-
sisted chiefly of a mild-to-modei'ate degree of psychoneurosis, plantar warts,
various orthopedic conditions of the feet, and partially disabling wounds of the
lower extremities.

In most instances, these patients did not have a normal gait even after four
to eight months following their initial exposure. They either walked on their
heels, on the lateral edges of the feet, or kept the toes extended .so that they
did not participate in weight bcailng or propulsion. All of them comjilained
of the inability to walk more than i/o without develojiing severe aching
and burning in the feet. IMany of the patients .still demonstrated an annoying
hyperhidrosis. which required clianging socks as often ;is two or three times
a day, and other findings indicating exce.ssivc .symiial belie activity, such as cold,
<“yanotie feel. Exaggeration of symptoms, particularly in the ea.se of sweating
and swelling of the feet, was frequently noted during hot weather. .Some of
the patients described a neuritic type of pain at rest and also numbnc.ss of one

ABRAMSON ET AL. : TRENCH FOOT

69

or more toes. Occasionally liypesthesia on the plantar surfaces of the toes and
adjoining portion of the foot was still present. For the most part, the skin on
the sole of the foot was delicate, probabF'' because the patients in this group
walked very little, in order to minimize the associated pain.

Except for two patients with minor lesions and good recovery and one who
was transferred to an amputation center, all others with a history of deep
gangrene and subsequent loss of tissue were also included in this group. Most
of them had experienced a severe attack of trench foot and at the time of their
disposition still displayed such sequelae as hj^perhidrosis, extreme coldness and
cyanosis of the feet, and manifestations of definite neuritic involvement, besides
the loss of toes or portions of the feet.

FOLLOW-UP STUDIES

Recent!}’ a questionnaire was sent to the first 250 patients in the group re-
turned to emlian life for the purpose of obtaining information concerning their
progre.ss in the interval. One hundred eighty-eight replies were received, and
the data have been analyzed. It is intended to continue this study at three- to
six-month ]ieriods in order to determine the residuals of trench foot which per-
sist, and whether or not indi\ddual;5 vith this condition become useful memliers
of their community again.

Prom an examination of the questionnaires, it was found that 68.3 per cent
of the patients obtained jobs within an average of 4.2 Aveeks after being dis-
charged from the Aimiy. Four per cent enrolled for courses in technical schools
and colleges, while 27.7 per cent had no job at the time of idling out the ques-
tionnaire (approximately two and one-half months after they had left the hospi-
tal). Forty -nine per cent of those who were working still had the job they
originally obtained. Thirty-two per cent of the entire group, including those
vdthout jobs at present, had to change positions from one to three times. As
%vill be noted in Table IV, A, a great proportion of the men had jobs requiring
physical labor, while only a .small number were doing a sedentai}* type of work.
For the group as a whole, the men spent an average of four hours on their

Tabi.e JV. Evaluation of Progress of Patients APFKO.xuiATELy Three Months After

Eetukn to Civilian Life

A. Types of Occupation

type j % of cases 1

1 type 1 % OP CASES

Farming and gardening 15.4

Cab or truck driving 14.6

Machinist or iielner 15.5

Factory Avorker 3U.o

White-collar job 24.0

- 7? SV 7 Tipio 7 ns Which Pcvsist in- tfw

symptoms I % OP CASES

SY’JtPTOMS ! % OF CASES

Burning sensation

Hyperliidrosis 63

Blister formation 26

Tenderness, sole of foot CO

Dermatophytosis 28

Sivelling 59

C. Ahilitv to Walk

DISTANCE - ■ ) % OF CASES

1 DISTANCE i % OF CASES

■ Less than Yi mile 12.9

Vr mile 12.1

% riiile 17.2

% mile 8.7

1 to 1% miles 3.3.7

2 to 3 mile.s 15.4

70

ATilElUCAX HEART JOURNAL

feet, daily. Twenty-two per cent of them were able to do their ,iob as well a.s the
man working next to them who had no physical disability, while 7S per cent were
not.

With respect to their medical status, a great proportion of the patients still
had numerous complaints (Table r\^ B). Their ability to walk ranged from
less than 3/^ mile to as much as 2 or 3 miles (Table IV, G). Forty-seven per
cent of the patients stated that they had observed no improvement in their con-
dition since thej’’ had left the hospital, 43 per cent noted slight improvement,
and 10 per cent noted more marked improvement.

SUiMMARY AND CONCLUSIONS

1. The later sequelae of trench foot were studied in a series of 633 soldiere
will) valuing degrees of involvement of the feet.

2. Ninety-four and two-tenths per cent of the patients had one or move
cxjiosures but never developed gangrene.

3. Five and eight-tenths per cent of the patients developed gangrene with
the loss of deep 1 issues of the feet.

4. No apparent correlation could be obtained between the duration of the
initial exposure and the seventy and persistence of the condition. Similarly,
there was no tendency for the patients with a histoi’y of frostbite to develop a
more severe ease of trench foot.

5. Shortly after exposure, the feet were swollen and discolored and showed
vesicle fonnation, desquamation of the sole, and hyperhidrosis. Such com-
plaints as pain, numbness, and paresthesias weim frequently present.

6. The sequelae of ti-eneh foot were divided into three groups, of which
one dcmonstraled findings indicating excessive sympathetic activity, the second,
a clinical piclure suggestive of some type of peripheral nerve involvement, and
llie third, signs and symptoms common to both of the other two groups.

7. Vai’ious tests were performed on the group of patients ivitli signs of
excessive sympathetic actirity but without gangrene. These procedures sup-
ported the view that no occlusive vascular disease wms present in the later stage
of uncomplicated trench foot.

S. Frequently, no correlation could be made beriveen objective findings and
complaints experienced by the patient. In some cases, practically no signs of
excessive vasomotor tonus were present, and the feet looked normal on inspec-
tion : still the patients walked on their heels or along the lateral borders of their
feet, because of tendemess in the soles. They also had various types of
l)aTestliosins. On the other hand, some indiriduals showed signs of cxce.ssivc
.sympaliu'tic activity, sucdi as cold, wet, cyanotic feet, or they even had super-
ficial gangrene, without any indication of nerve involvement. Their gait was
normal ; many of them were able to walk a mile or two without experiencing
any discomfort.

fi. The treatment of the sequelae of trench foot was divided into two cate-
gories, namely, medical and surgical therapy and the reconditioning jirogram.
I he medical and surgical treatment was directed toward removal of the dead

AB1?AMS0N ET AL. ; TRENCH FOOT

71

epiderjnis, couiiteraciing the stiffness of the toes and atrophy of the small
muscles of the feet, reducing the hyperhidrosis, minimizing the pressure applied
to the tender soles of the feet on 'walking, and decreasing the swelling.

If amputation -was necessary, conservatism -was practiced, and every effort
was made to control infection. When large skin defects existed or "when skin
was lost on \veight-bearing surfaces, various types of skin grafting were found
lo be helpful. Sjonpathectomy appeared to have a definite place in the treat-
ment of only certain selected cases; in the majority of instances it was not in-
dicated.

10. The purpose of the reconditioning program was to build up the general
physical condition of the patient first and then to concentrate on the feet. TJic
skin of the feet was hardened by such procedures as calisthenics in the pool and
gymnasium, walking, and bicj^'cling. At the same time, the small muscles of the
feet were exercised in order to counteract the atrophy.

11. After the completion of the reconditioning program, 33 per cent of the
series were returned to a limited type of duty. ]\Iost of the men in this group
had a nonnal gait, -were able to walk a mile or more, had no signs of hyper-
hidrosis, atrophy of muscles of the feet, or stiffness of the toes. Sjnnptoms in-
dicating nerve involvement were minimal, the mental outlook of the patients was
satisfactoiy, and they did not liavc other medical or surgical defects.

>Sixty-seveu per cent of the series were discharged to civilian life. i\Iost of
the men in this group demonstrated signs of excessive sympathetic activity,
walked poorly and only for short distances, complained of various tj^^es of
paresthesias, or had lost portions of their toes and feet as a result of gangrene.

12. In conclusion, it is obvious from this stud}’’ that trench foot is associated
with a long period of at least jDartial physical incapacitation. The exact dura-
tion of this interval can only be determined bj'^ follow-up studies. In view of the
fact that the sequelae of trench foot are aggravated by extremes of environmental
temperatures, patients with this condition should, whenever possible, live in a
place where a moderate climate exists most of the year.

The authors AAush to express their appreciation to the many medical officers in ov^seas
medical rmits, who first treated the patients in tliis series, and to the vanous ward offices
at the Mayo' General Hospital, and among them, particularly. Captains H. H. L^npert, ±t. H.
Smith, P. B, Olsson, and R. Murray, who have helped generously in the study. They are also
indebted to T/4 Adolph Schwartz and Cpl. Jacob W. Fite for their valuable assistance in
the compilation of the data which form the basis for this report.

REFERENCES

h Pickering, G. W.: On the Clinical Recognition of Structural Diseases of Peripheral

Vessels, Brit. M. J. 2: 1106, 1933. ocrr

2. Priedman, N. B.: The Pathology of Trench Foot, Am. J. Path. 387, l"^-

3. Patterson, B. H., and Anderson, F. M.: War Casualties From Prolonged Exposure to

Wet and Cold, Surg., Gynec. & Obst. 80: 1, 1945.

4. Preis, E. D.: Personal communication. ^ -m i-niA c...,

o. vShumacker, H. B., Jr., and Abramson, D. I.: Sympathectomy in Trench Foot, Ann. Surg.

(In press ^

6. Edwards, .1. C.’ Shapiro M. A., and Ruffin, J. B.: Trench Foot, Report of 351 Cases,

Bull. H. S. Army M. Dept. 83: 58, 1944. _

7. ''Abramson, D. I., Fierst S. M., and Flachs, K.: Evaluation of Local Vasodilator Effects

, of Acetyl-beta-mkhylcholine Chloride (Mecholyl) by Iontophoresis, An. Heart J.
23: 817, 1942.

THE CONSTRUCTION OP THE CARDIAC VECTOR

R. F. Hill, M.S., M.A.'^

New Orleans, La.

A CERTAIN problem in connection with the construction of the cardiac vec-
tor representing the “manifest potential” has recently come to our atten-
tion.^ Inasmuch as this problem may be a source of t roulile and misunderstand-
ing to other workers, and since it involves conceijts which perliaps need furtlier
clarification, we shall discuss it in some detail.

The prolilem can be illustrated best by an example. Suppose the values of
the potential at the right arm, left ann, and left leg are measiu’ed either by
Wilson’s common terminal technique* or by Goldberger’s augmented-potential
method, and suppose we find that :

Vn = -3
Vr, = +10
Vp = -7.

Then if we either measure the limb lead potential differences simultaneously
or obtain tliem from the unipotential values, we would find, of course, that :

Cl == +13

Co = "I
cl = -17.

Now let us construct the cardiac vectoi', using botli sets of values, and let us call
the con.struction using Cj, Co, and Cg iVIethod I, and tiie eon.struction using I'n-
Vr,. and V,- l^Icthod II.

]\retliod I, following Bayley’s notation,'* is shovTi in Pig. 1. The three axes,
representing the tlirce limb lead directions, make angles of 60° with each other.
Calling the cardiac vector E, we find that it has a magnitude of 17.8 units and
makes an angle of 42° with tlie horizontal.

llethod II makes use of the triaxial system formed by OR, OL, and OF
in Einthoven's triangle (Fig. 2). 0 is the center of the tinangle, at wliieh the
(ail of the cardiac vector is located, and constitutes the origin of this second .sys-
tem. The new axes also make angles of 60° Avith each other, although thej' do
not have the same directions as those of Slethod I. Actually, the second triaxial
.sy.stem consists of a rotation of the first through an angle of 30°. Using the

Kroiii tlip Dfjiarttncnt of Phyjslolofr>'. I./ouis!nna .State ITnlver.'jity School of Mctllclnc, N'-w
Or!> nn“. tji.

KcccKcU for pubUc.T.tlon Aup. 23, 1915.

•Now in the Physic? iJcjiartmcnt, Mcniorlnl Hospital, New VorU, N. Y.

74 .

AMERICAN HEART JOURNAL

values of Vr, Vi,, and Vr given previously, we construct as in ]\IcthocI I. 3
shows the vector constructed by jMethod II. This time tlie resultant vector has
a magnitude of 10.2 units, although it still makes an angle of 42° witli the hori-
zontal. Therefore, the result obtained by ]\Iethod I is 17.S units, which is
limes Jiigher than the result obtained by Slethod II, 10.2 units.

+F

Kip. 3. — CoTistnu’tion of K by MoUiod II. Vi: = —3. Vi. = -r 10. Vj- = -7. E is now 10.2 Oi'iV.

wJiilo a i.s .•-•till -la”.

To illustrate further, let ns .suppo.se Dial we actually know in advance the
magnitude and direction of E. To simplify the calculation, let E be IT.B units
and let it make an angle of 42° with the hoiizontal (Lead I). Tlien by rcvensing
the pixieedure of IMethod I, we obtain

r, -= -K3
f . = -4
=- -17.

The values of Vr, Vr, and Vr, obtained in a similar manner by reversing the
procedure of Method II. are

Vi. -- •= 17.4
\ u ■'•=^^ — ;).«3

\ j. cr-i —12.1.

HILL: CONSTRUCTION OP CARDIAC VECTOR 7k

I U

This is shown in Fig. 4. From these values, we see that

’ e, = +22.7

Go = — 6.8

C 3 = -29.5.

Evidently tee values of and e, are VT times higher than the values ch-
ained by the direct proiection of B on I^eads I, II, and III, or, what amounts
to the same thing, Vn, Vl, and Yj, are V 3 times higher than the originals.

Pig. 4. — Resolution of TO to find Vi„ Vit, and Vr- B is assumed to be 17.8 units, and a is 42°.

We find that Vi. = + 17.4, Vn = -5.3, Vr = -12.1.

To summarize : tlie cardiac vector as obtained by Method I is V 3 times
higher than the cardiac vector obtained by Method II. On the other hand, if
we start with a given value of E, then the values of e^,^ and obtained by di-
I’eet projection onto the limb leads turn out to be V 3 times loiver than the
values obtained by finding Vr, Vr, and Yp, followed by the necessary subtrac-
tions.

It is natural to ask which method is correct. The answer is “both.” In
order to explain this apparent discrepancy, we shall have to investigate the
nature of what we are doing when we make these constructions. The present

76

AMERICAK HEART JOURNAL

paper is an attempt to clarify some misconceptions whieli appear to be fairly
common.

Wilson and liis co-workers,'’ Bayley,® and others have explained the nature
of the cardiac vector and of the electric field which it produces. The reader is
referred particularly to the section of Bayley’s paper® which deals with vectors
and electricity. For present purposes, we need only start with the concept that,
at the heart, there exists an electrical force, which has at any instant a mag-
nitude and direction and which can, therefore, he represented by a vector. Sur-
rounding this vector is a field udth a potential distribution, every point of wliieh
possesses a definite potential. By the potential of a point we mean the work
which would be done if we brought a hypothetical unit positive charge from
an infinite distance to the point in question. By the potential difference be-
tween any Uvo points, we mean the work which would be done if we moved this
charge from one point to the other. If we say that the potential or the potential
difference is positive, we mean that we have had to do work and expend energy'
in this transit. If we say that it is negative, we mean that the electric field
has done the work for us. Now work is not a vector quantity because there is
no direction associated with it. Thus, in Fig. 5, the work done in going from
A, which has a potential of -f5, to B, which has a potential of 4-10, is -fU units,
regardless of how we get fi’om A to B. There are certain parts of Part II where
the field will do the work for us and other pails where we will have to do the
work; but the excess of what we do over what the field does, is always five units.
Hence, it should be evident that neither the potential at a point such as Vn, Vi.,
or Vp nor the potential differences such as c,, Cj, and involve a special direc-
tion, and that they are not, therefore, vectors.

It may be well to take up at this time another point, which explains why
C3, a- fact which has nothing whatever to do with Einihoven’s triangle.
Instead of taking two ])oints in the field, let us take any three jioints and lot us
give them any potentials we choose. Further, let us call them B, L, and I',
oriented quite at random (Fig. 5, b). Let us go from B to L to F and back to B,
calling the work done between B and L, c„ between L and F, e.j, and between F
and B, e.. (in order to retain the electrocardiographic notation), c, is then -8,
wliich means that in going from B to L the field }iel])s us by doing S units of
work; fg is 4-112, which moans that in going from L to F we have to do 112 units
of work; e.. is -104, which means that in going from F to B the field docs 104
unit.s of work. The net amount of work done is -8 312 - 304, which is zero.

This is a general fact, and it tolls us that whenever we go around a closed loo]),
of any shape, and retimi to the starting point, the net amount of work done is
zero. This is true for any numbei' of stopping points above two, the only con-
dition bciTig that we get back to the starting point.

In the exam))lo above, wo have seen that a, 4- e.. c., = 0. Now, if wo ar-

bitrarily I'cver.'jc the sign of the work done between any two poijits, then ob-
viously this work will equal the sum of all the other work done. That is exactly
what is done in elect locardiography. The attachments to the galvanometer are

HILL; CONSTRUCTION OP CARDIAC A^GTOR 77

sucli that ^Ae measure the work done (potential difference) in going from F to R

instead of from E to F. Tlicrefore, e, is arbitrarily given a negative sign and
we obtnin

~ ^2 + C3 == 0 or
~ ^3 ^ 2 ’

R=+3

Pif?. ;■). — a. Two points in a scalar potential flelcl. h, R, h, and F are any three points in a

scalar potential field.

To return, then, to our original problem, in electrocardiography, R, L, and
^ are not oriented at random but are regarded as being located at the apices
of an equilateral triangle. From what has been explained above, it is clear that
none of the six quantities Vl, Vk, Vf, Oi, 6o, and Cg has anj’’ necessary direction
associated with it. These quantities are not vectors, but scalars, and, like all
scalars, they can be added or subtracted in the same way that we can add two
apples to eight apples or subtract two apples from eight apples. Therefore, it is
possible to define as Vl - Vr, et cetera.

However, if we assign definite directions to these quantities, we can treat
them as vectors. This is done, of course, by assigning to e., and the direc-
tions of the limb leads, i.e., the directions of the sides of the equilateral triangle ;
and by assigning to Vr, Vr, and Vf the directions OR, OL, and OF, respectively
(Fig. 2). Now when these six quantities are transformed into vectors, they

78

a:merican heart journal

must obey vector la^Ys. They can no longer be simply added or subtracted. To
illustrate what this means : if 1 is a scalar, then we can add 1 and 1 and obtain 2 .
If 1 is a vector, then the addition of two such vectors will give a resultant of 2
only when the two vectors are pointing in the same direction. If they make, for
example, an angle of 90° vdth each other, then their sum is not 2 but \f2.
Hence it follows that, after becoming a vector, quantity is not necessarily
equal to Vl - Vp. We have, in fact, given these six quantities six different diwc-
tions.

R L

and n. Thp.se mapnitudes are pivcn in the text.

Tlie purpose hi trausiovm'mg tlie.se quanlities into vectors is to enable us
to treat these A’cctoi-s a.s the pi'o.ieetions or components of the cai’diac vector 15,
which we call the “manifest potential difference’' or tlie “electrical axis” of
the heart. Tliis is legitimate enough. Now, if is to be the projection of E
in the direction of limb Lead I, then V i. - Vr> which has been defined as equal
to Cl, should also be the projection of E in the direction of Lead I. But the
definition of as Vl - Vp was based on the essentially scalar nature of these
quantities and does nof carry over when they become vectors. This means that
if, as in Pig. ], = +10 and Vn — -3, c, does nof equal +13. Similarly, C; and

C 3 must be dealt with as vectors and not as sealai's. If Pig. 3, constructed for
vfclor values of Yi,, Yr, and Yp is correct, then Pig. 1 must have been con-
structed from the wi-ong vector values of c,, c.,, and and must therefore lie in-
correct with respect to Fig. 3. On the other hand, if the vector values r, -L'h
#2 -4, atid == ~37 are correct, thereby making Pig. 1 correct, then l''’ig. 2

is incorrect because we have used the wrong values for Yu, and Yp.

?IILL: CONSTRUCTION OF CARDIAC MiCTOR

79

To find our way out of this difficulty, we only need find out liow the com-
ponent of E ill the direction of Lead I is related to tlie difference between tlie
components in the directions of OL and OF. In other words, how is rector e,
related to the rector (Vl - Vp) ? Vectors Co and must be similarly studied.
As a matter of fact, these relationships already have been worked out, although
not in the exact form in which thej' apply to this problem.' Pig. 6 .should need
no exjilanation. We must only keep in mind that all of the quantities used below
are to be thought of as vectors. As usual, a is the angle between B and Lead I.
Our six vectors are related to E and a by the following relationships :

Cl = E cos a

e., = E cos (a - 60°)

el = E cos (120° - a)

Vn = E cos (210° - a)

= E cos (a + 30°)

Vp = B sin a

The only other relationship we need is the familiar trigonometric one, cos
(A ± B) == cos A cos B + sin A sin B.

- Then

Vr/- Vn

Vn - Vn

Vn-Vn
Similarly.

Yjj, _ Vn == E I sin a - cos (210° - a) | , and

Vp

But 62 -

: Multiplying both sides by V 3, we get ^

= B cos q: + sin a .

Vp - Vn = 62

Similarly- ' _

' ' Vp _ Vj^ = E sin a. - cos (a + 30°) , and

Vp
But 63 =

q 1 —

_ Vn = E -v V 3 cos a .

~ 1 -rr • 1

= cos (120° - a-) = E V 3 sm a - cos a

3 1 —

- Vn = E -y sin a + y V 3 cos a I .

= E cos (a - 60°) = E j cos a + -“ V 3 sin a .

== E cos (a + 30°) - cos (210° - a) 5

Z ^ 2

= E cos a- - sin a +-J^ cos a + ^ sin a

— E cos a • V 3 — Cl V 3.

80

AJIERICAlNr HEART JOURNAL

Multiplying both sides by V 3, we get
y 3 Cg = E

^ sin a ^ V 3 cos a

Yp - Vi, = Cg '\fW.

Summarizing,

Vi, - Vji == fi,

Vp - Vr = e, yT
- Vl = Cs V 3

The reason for the discrepancy betu'cen Figs. 1 and 3 is now obvious.
Both constructions are perfectly’- valid but differ from each other by the pro-
portionality constant V 3. Therefore, two procedures are open to us: (a)
We can use IMethod I, unchanged, on the limb lead potentials. However, if we
then wish to use j\Iethod II on Vl, Vr, and Vp, w'e must make an adjustment
either bj' multipljdng Vr, Vr, and Vp each by V 3 before constructing E, or by
constraeting E first and then multipljdng its value by (b) We can use

j\Iethod II unchanged on Vr, Vr, and Vp. However, if we then wish to use
jMethod I on e^, c,, and Cg, we must adjust either by dividing these values by
before constructing E, or by constructing E fii’st and then dividing it by V 3.

Since the equations defining these vector relationships contain no angles,
either method, unaltered, ivill give the correct orientation of E.

As Wilson® and othci’s have pointed out, the construction of the cardiac
vector, E, is a very useful tool in clinical analysis, even though the vector so ob-
tained does not give the actual magnitude^ but only a quantity proportional to
it. We have discussed in this paper another proportionality factor which must
be taken into account wdien different methods of construction are used. To put
the matter in simple comparative terms, it is as though ]\Iethod I gives the value
of E in feet, and IMethod II in yards, -whereas E might really be expressible in
miles. If we imagine that the relationship between the mile on the one hand,
and feet and yards on the other, is unloiowm or unmeasured, then -we -wdll get a
good picture of the actual significance of these constructions.

SUMMiVBY

1. Two methods of constructing the cardiac vector, E, differ from each
other by a factor

2. The quantities measured in electrocardiography are essentially scalar
in nature; from this fact the independence of the relationsMp + Cg — e,, of
Einthoven’s triangle, follows.

3 . The significance of a transformation of Vr, Vr, Vp, Cj, c,, and Cg into
vectoi’s was discussed. The relationship behveon these vectoi’s -was obtained and
it wa.s shown that both methods of construction arc valid and equivalent and can
be equalized, if one makc.s certain adju.stments to account for the difference in
orientation of the two ti-iaxial reference systems.

The author tvivlics to thank Dr. Emnmnuel Goldbcrgor for callinj; the problem to her
a ttentio n and Dr. Richard Ashman for hi.s rncourngement.

•The actu.n mannltudo, as ii.scd here, refera to the majmttudC! of the projection of the
rpfttinl \ccior on tli.- rmntal plane. It was not ncccs.snrj'. In Uie above analyfll.>i, to discuss the
tbrvt'-diincn-ional cardiac vcclor.

til

HILL: CONSTRUCTION OF CARDIAC VECTOR
REFERENCES

81

1. Goldberger, E.: Personal communication.

2. Wilson, F. N., Johnston, P. D., Maeleod, A. G., and Barker, P. S. : Electroeardiogi’ams

That Eepresent the Potential Variations of a Single Electrode. Am. Heart J. 9:
447, 1934.

3. Goldberger, E.: A Simple, Indifferent, Electrocardiographic Electrode of Zero Potential

and a Technique of Obtaining Augmented Unipolar, Extremity Lead.s, Am. Heart
J. 23: 483, 1942. .

. Bayley, E. H.: On Notation, Am. Heart J. 25: 33, 1943,

. Wilson, P. N., Maeleod, A. G., and ’Barker, P. S.: The Distribution of the Action
Currojnts. Produced - by Heart Muscle and Other Excitable Tissues Immersed in
Extensive Conducting Media, J. Gen. Physiol. 16: 423, 1933.

6. Bayley, E. H.: On Certain Applications of Modern Electrocardiographic Theory to the

Interpretation of Electrocardiograms Which Indicate Myocardial Disease, Am.
Heart J, 26: 769, 1943.

7. Wilson, P. N. Maeleod, A. G., and Barker, P. S.: The Potential Variations Produced

by the Heart Beat at the Apices of Einthoven's Triangle, Am, Heart J. 7: 207,
1931.

8. Wilson, P. N., in Stroud, W. D.; Diagnosis and , Treatment of Cardiovascular Disease,

Philadelphia, 1940, P. A. Davis Company, vol. 1, p. 570.

THE INCIDENCE OF PALPABLE DORSALIS PEDIS AND POSTERIOR
TIBIAL PULSATIONS IN SOLDIERS

Ax Analysis of Over 1,000 Infantry Soldiers

Captain Jacob J. Silyerman, M.C.

Arjiy of the United States

P alpation for pulsations of periiJieral arteries is an important clinical
procedure. In the study of peripheral vascular diseases the presence or ab-
sence of a pulsation often gives a great deal of information. Pulsation may he
absent in spasm, or as a result of organic changes in the palpated vessel. It is
not sufficiently understood, however, that the absence of pulsation may also
indicate a nonnal anatomic deviation. Tlie radial arteiy pulsations are easily
palpable and in normal individuals are rarelj’’ absent.

It has been a widely accepted opinioiP that the dorsalis pedis and posterior
tibial pulsations almost always can be palpated in normal individuals, or at least
are very rarely absent. Buerger^ studied 200 patients in whom the presence of
peripheral vascular disease was carefully ruled out and found only in one in-
stance an absence of the dorsalis pedis pulsation. This low incidence of absence
of pulsations (0.5 per cent) compares favorably Avitli the findings in a similar
stud}'' of 381 patients by Erb,- In Erb’s series an absence of both po.slcrior
tibial pulsations was noted in two patients, and an absent pulsation of the
dorsalis pedis and posterior tibial of one foot was noted in two patients. An
absent pulse wa.s, therefore, observed in less than 1 per cent of tho.se patients
who presented no evidence of peripheral vascular disease.

This low incidence of absent pulsations in normal individuals has been
challenged by other investigators. Morrison,^ in an analysis of 1,000 individuals
without symptoms of circulatory afi'ections of the extremities, found an in-
cidence of 19 per cent with absent pulsations of the donsalis pedis and posterior
tibial arteries. It should be mentioned that in llorrison’s study two-thirds of
the patients were women and that the ages varied widely. ReielF studied 500
healthy individuals and noted an absence of the dorsalis pedis pulsation in 4 per
cent and an absence of the posterior tibial pulsation in 5 jicr cent of the patient.s.
In an additional S per cent of the ])atients the dorsalis pedis jnilsation was found
in a position other than the usual one. In Sehneyer's- analysis of 500 controls
there was an absence of pulsation in 17 per cent of the men and 29 per cent of
the women.

To supply further information on Ibis problem the dorsalis pedis and pos-
terior tibial pulsations were studied in 1.014 soldiers at an Army Infantry
Training Center. Each .soldier liad completed his- basic infantry t?'aining: the

til til.' ttiimial iin>.-UnK lA tlu- It'.in lUtirl A? o< iiition, Smi Fniticltco,

CaUf., JuTi.' 211, jnic.

Kx-fiVt’O for iniblioation S'^pt. 1 , 1015.

S2

SILM5RMAN : PALPABLE DORSALIS PEDIS A^^D POSTERIOR TIBIAL PULSATIONS S3

examination was part of the processing for overseas duty. As far as could be
ascertained no soldier presented circulatory complaints of the lower extremities.
The average age was 20 years ; over 90 per eent of the soldiers examined were
under 22 years of age. All the examinations were performed by tlie same med-
ical officer. The subjects were divided into four groups, A, B, C, and D. BacJi
group was examined at a different session, on a different day, but at a .similar
hour. Gfroups A, B, and C were composed of white men, and Gfroup D was com-
posed of Negroes. To insure accuracy Groups B and C ivere checked by another
examiner. The pulsations were graded as “palpable"’ or “not palpable.”
Where a pulsation was weak, faint, or found at a slight distance from the usual
location, it ivas considered palpable.

FINDINGS

A summary of the four groups examined is given in Table I, Of the 1,014
soldiers examined, 898, or 88.6 per eent, had a palpable right dorsalis pedis, and
116, or 11.4 per eent, liad an ab-sent right dorsalis pedis pulsation. In the

Table I. Combosite Table of Pulsations

DORSALIS PEDIS
RIGHT

POSTERIOR TIBIAL
RIGHT

DORSALIS PEDIS

LEFT

POSTERIOR TIBIAL
LEFT

1 NOT

palpable palpable

PALPABLE

NOT

palpable

PALPABLE

NOT

PALPABLE

NOT

PALPABI.E PALPABLE

A

330

47

370

(wliite)

377 '

87.5%

12.5%

98.1%

B

234

38

263

(wtiite)

272

86.0%

14.0%

96.7%

C

230

29

255

(white)

259

88.8%

11.2%

. 98 . 0 %

D

104

2

97

(Negro)

106

98.1%

1.9%

92.5%

(A, B, C, D)

898

116

985

1,014

88.6%

11.4%

97.1%

7

326

51

373

4

1.9%

9

86.3%

237

13.7%,

35

98.9%c

2i'.j

1.1%

7

3.3%

4

87.2%

213

12.8%

46

97.4%

252

2.6%

r»

/

1.5%

9

82.2%

101

J7.8%

0

.97.3%

97

2.7%

9

7.5%

95.3%

4.7%

91.5%

S.5%

D) 898 1J6 985 29 877 1.37 987

88.6% 11.4% 97.1% 2.9% 13.G% 97.3%

Table II. Table of Absent Pulsations in More Than One Akterv

GROUP

A

(white)

377

B

(white)

272

C

(white)

259

D

(Negro)

, 100

TaTbTcT^

1,014

TIBIAL

S’OT PALPABLl
BIGHT FOOT
0

0 . 0 %

2

0.7%

0

0 . 0 %

2

0 . 2 %

DORSALIS PEDIS ^
AND POSTERIOR
TIBIAL

NOT PALPABLE
LEFT FOOT 1

DORSALIS PEDIS
NOT PALPABLE
BOTH FEET

1

25

0.3%

6.6%

1

28

. 0.4%

10.3%

1

22

POSTERIOR

TIBIAL

NOT PALPABLE
BOTH FEET

3

0 . 0 %

3

0.3%

0.9%

76 _
7 . 0 %

7.5%

17

1.7%

AilERICAX HEART JOURNAL

left foot. S77 (S6.4: per cent) had a palpable doi-salis pedis pulsation, and in 137
; I3.G per eeat) this pulsation was absent. The posterior tibial pulsation on the
ripht side was palpable in 985 (97.1 per cent) and absent in 29 (2.9 per cent).
On the left side, the posterior tibial pulsation was palpable in 987 (97.3 per cent)
atnl absent in 27 (2.7 per cent) .

Tlic miniber of absent pulsations in more than one artery is shown in Table
11. Of the 1,014 soldiers examined, only two soldiers had an absent dorsalis
pedis and an absent posterior tibial pulsation of the right foot, and in only three
-soklieis were those same pulsations absent in the left foot. There were 76
.soldiers with an absent dorsalis pedis pulsation in both feet, an incidence of 7.o
per cent. In 17 soldiers there was an absence of both the posterior tibial pulsa-
tions in both feet, an incidence of 1.7 per cent.

T.\ni,r, III. Taria: of CoMPAntsox of Pulsation's in White and Negro Soldiers

j

i DORSALIS PEDIS
RIGHT

i POSTERIOR TIBIAL

1 RIGHT

DORSALIS PEDIS ’
LEFT 1

POSTERIOR TIBIAL
LEFT

RACE

1

1 P.M.PADLE

NOT '
PAI.PABLE

1 PALPABLE

P.>VLPABLE

NOT

Wliilc

f00.S)

Negro

(tarn

79t

S7.-l%

104

OS.1%

114

12.G%

2

L9%

sss

97.8%

97

92.5%

20

2.2%

9

7.5%

770

85.6%

101

95.3%

132

14.5%

1?%

890

98.0%

97

91.5%

18

2.0%

9

8.57o'

The frcciuency of pulsations in the white and in the Negro soldier is shown
in Table TIT. A significant difference was found in the two races. Whereas
(lie right dorsalis pedis pulsation was absent in 12.6 per cent of the white men,
this inilsalion was absent in only 1.9 per cent of the Negroes. On the left side
of the doi-salis pedis pulsation was absent in 14.5 per cent of the white men and
in only 4.7 ])er cent of the Negroes. The situation was reversed when the pos-
terior tibial pulsations were examined: approximately 2 per cent of the pos-
t«‘ri<ir tibial inilsations were absent in the white group and 8 per cent in the
Negro grmip. When the absence of pulsation in more than one arteiy was stud-
icii (Table IV), the wliitc soldici-s .showed a higher percentage of absence of
both <hnvalis ]icdis pulsations, whereas the Negro soldiers showed a higher per-
mitage of absence of hilatcrnl posterior tibial pulsations. Absence of both a
dor-salis pedis and a posterior tibial pulsation in the same foot was very nnusiial.
This oi-i-urrcd only five limes in the 1,014 soldiers examined. In only one soldier
of the entire series was the ahsence of pulsation of both the doi-salis pedis and
posterior tibial in both feet obsoiwcd.

T.\T:!,r. tv. T.uiLi: or Comr.muson of Ad.sent Pul.s.ations in iloRF. Than One Artery of

W'niTi; AND Nmro Soldiers

LKi'}:

i IT-UIS I

dorsalis PI'.DIS

1 .'Nil POSTKRIOP.

1 AND POSTF.RIOR

■ Tint At,

1 TIBIAL

dorsalis it.dis

POSTERIOR TIBIAL

NOT PAI.P.MU.R 1

1 NOT PAI.PABI.P.

NOT PALPABLE

NOT PALPABI.E

■. ' liokt yiViT

1 LEIT FOOT 1

BOTH feet 1

, BOTH FEET

0.3ci

0

O.OCc

1

/o

1 . 0 %

.s

7..o%

SILYERJIAN: PALPABLE DORSALIS PEDIS AND POSTERIOR TTBLVL PULSATIONS 85

DISCUSSION

A clinical study of the incidence of pulsations is subject to certain criti-
cisms. The interpretation of a pulsation is subjective, and its accuracy depends
to a large extent upon the efficiency and experience of the examiner. Moreover,
the environment in which the examination is performed will influence the results.
A cold room, for example, maj’’ cause a barely palpable vessel to become im-
palpable. Emotional factors may influence the results, and in anxiety states the
caliber of the blood vessels may be profoundly reduced. The physical condition
of the patient at the time of the examination may affect the results. Such other
conditions as a deformity of the foot, varicosities, edema, or obesity may make
it difficult to palpate a normal vessel. Most studies dealing with tiiis prob-'
lem include women, thus introducing further variables. It is important to
emphasize that this study was performed on a group of healthy, young soldiers
chosen for the infantr3^

The. arterial blood supply of the foot is derived mainly from two arteries,
the anterior tibial and the posterior tibial. The dorsalis pedis artery is really
a continuation of the anterior tibial artery, extending downward to the proximal
portion of the first intermetatarsal space. The posterior tibial artery is a con-
tinuation of the popliteal artery and extends downward to the groove between
the internal malleolus and os caleis. It is these two arteries with their extensive
series of anastomoses which insure a proper arterial supply to the foot. In man,
however, this architectural arrangement is subject to many variations. As
Reich® has pointed out, man differs from all other primates in this arterial
distribution. In primates other than man, the blood supply of the foot comes
directly from the femoral artery by way of a saphenous artery. Tliis saphenous
artery, not found in man, continues as the dorsalis pedis arteiy and gives off a
posterior branch supplying the plantar aspect of the foot. This more direct
arterial supply of the foot seen in other species of primates is therefore subject
to less anatomic variation.

A normal variation of the arteries of the foot has been noted by anatomists.
According to Gray^ the dorsalis pedis artery may be larger than usual to com-
pensate for a deficient plantar vessel, and “in 12 per cent of the bodies examined
the dorsal pedis artery was so small as to be considered absent.” Although no
figures were given, Gray^ noted that the posterior tibial artery was “not infre-
quently smaller than usual or absent.” Clinically, therefore, one should nor-
mally expect to encounter absent dorsalis pedis and posterior tibial pulses in a
small but definite percentage of cases. It was somewhat surprising, however, to
find the incidence so high. Moreover, the incidence seemed to varj^ within the
white and Negro races. This difference in frequency of pulses from a racial
standpoint was commented upon by Reich,® who found, for example, that 4.9
per cent of the Japanese on whom observations had been made had an absent
posterior tibial arteiy, as compared with 8.7 per cent of Europeans. In tliis
study it was found that an absence of the dorsalis pedis pulse was decidedly more
common in white persons than in Negroes. The reverse was true of the posterior

so

AMERICAX HEART JOURN'AT,

tibial ])iilsation. Tl "vvas iiiuisnal to find an absent posterior til)ial in white
soldiers (2 per cent), whereas in the Negro soldier an absent posterior tibial
]>ulse was more conunon (8 per cent). Regardless of race, when the domlis
pedis pulsation was absent, a good posterior tibial was invariabl.y found; and
similarly when the posterior tibial pulsation was absent, a good doi-salis pedis
was found. In only five instances (0.49 per cent) of the entire series of 1,014
subjects was this finding violated. This is understandable when one considers
the arehitectui'al arrangement of the arteries of the foot. The collateral circula-
tion of the foot is dependent upon an adec]nate anastomosis of the po.sterior tihial
and dorsalis pedis arteries. It is apparent, then, that a reduction in the size
of the dorsalis pedis arteiw, for example, will be accompanied by a correspond-
ing increase in the size of the posterior tibial artery. From a practical stand-
])oint it is well to remember that in normal individuals an absence of both the
dorsalis pedis aiid posterior tibial pulsations on the same side is anatomically
unsound and decidedly uncommon. An absent doisalis pedis and posterior
tibial pulse on the .same side would, therefore, seem to have more clinical sig-
nificance than an absence of Inlateral dorsalis pedis or an absence of bilateral
posterior tibial pulsations. The order of importance to be attached to normal
absence of pulsation in soldiers of the two races is shown in Table V.

Taik.k V. Pia,s.vn().v.s ok Foot Akkanock AccoRm.vo to Ordkr ok Ahse.vck

•VIUTE

XKono

1, l.cft dorpuli.s pedis

2. Itiglit dor.s!ili.s pedi.e (12.0%)

a. Right and left dorsalis pedis (8.3%)

4. Right posterior tiltinl (2.2%)

.A. Left posterior tihial (2%)

li. Right and left post(Tior tihial (1%)

7. Left dorsali.s pedis and left po.sterior tib-
ia) (0.3%)

5. Itiglit dorsalis jtislis and right posterior
tihial (0.2%)

• 1. I^eft posterior tii)ial (8.5%)

2. Right posterior til)ial (7.5%)

3. Right and left posterior tibial (7.5%)
■1. Loft dorsalis pedis (4,7%)

5. Rigid dorsalis pedis (Lfl%)

0. Right and left dorstilis pedis (0.9%)_

7, Right dorsalis pedis !ind right posterior
tibial (0%)

8. Left dorsalis pedis and left jiosterior
tibial (0%)

.'=5U>M.MAR\’

1. The incidence of palpable doi'salis pedis and posterior tibial jndsations
was studied in 1,014 infantry soldiers; in over 13 pei‘ cent one or more pulsc.s
was absent.

2. The incidence of ])alpable ])ul.sations in these arteries was different in
white and Xegi-o soldieis. The postcrioi* tilual pulse Avas more fj’equently ab-
sent in the Negro, and the dor.salis pedis pulse wa.s more fi'cquently ab.scnt in the
white soldier.

3. Absence of both the dor.salis pedis and the posterior tibial pulses oii the
sjtmc side was Ttiost \mnsual. This combination occuiwed in only five instances
•if the entire scries.

4. The posterior tibial and donsalis pedis arteries in man are .subject to Avidc
anatomic variations. In interjircting an absent pulsation in the foot one should
be aware of tln-se normal variations.

0 \

SIL\T5RMAN : PALPABLE DORSALIS PEDIS AND POSTERIOR TIBIAL PULSATIONS 87

REFERENCES

1. Buerger, L.: The Circulatory Disturbances of the Extremitis, Philadelphia, 1924, W. B.

Saunders Co.

2. Erb, W.: Ueber das “intermittirende Hinken” und andere nervose Stdrungen in Polge

von Gefasserkrankungen, Deutsche Ztschr. f. Nervenh. 13: 1, 1898.

3. Eormijne, P.: Investigation of the Patency of Peripheral Arteries, Am. Heart J. 10:

1, 1934.

. Gray, H. : Anatomy of . the Human Bodj', ed. 24, Philadelphia, 1942, Lea & Eebiger.

. Morrison, H. : A Study ' of the Dorsalis Pedis and Posterior Tibial Pulses in One
Thousand Individuals Without SjTuptoms of Circulatory Affections of the Ex-
tremities, Ncav England J. Med. 208: 438, 1933.

6. Reich, R. S.: The Pulses of the Foot; Their Value in the Diagnosis of Peripheral

Circulatory Disease, Ann. Surg. 99: 613, 1934.

7. Schneyer: (Cited by Pormijnes) Deutsche med. Wclinschr. 50: 10.9, 1.924.

THE RATES OP ^’ATER AND HEAT LOSS PROISI THE RESPH^ATORY
TRACT OP PATIENTS WITH CONGESTIVE HEART FAILURE
^YHO WERE FROi\I A SUBTROPICAL CLI:MATE AND
RESTING IN A COlMPORTxVBLE ATMOSPHERE

G. E. Burch, M.D.^

New Orleans, La.

B ecause of the importance of the disturbances in water balance in con-
gestive heart failure, any knowledge of the nature of water loss from the
respiratory tract is significant. The dyspnea and accumulation of water in the
lungs in congestive heart failure makes a study of this sort even more interesting.
As shown previously,^ the rate of heat and water loss is influenced by the condi-
tions of the environment, particularly hot and humid environments. The latter
type of environment was found to disturb the patient in congestive heart failure
a great deal" thus further increasing the need of a study of water and heat
loss from the respiratory tract in heart failure. Such observations are wanting,
for a review of the literature revealed only one paper® concerned with such
studies. With these facts in mind, a study was rxndertaken to investigate
(luantitatively the rates of water and heat loss from the respiratory tract of
patients with congestive heart failure who re.sted sitting in a comfortable
atmosphere.

METHODS AND MATERIALS

The methods employed for the measurement of water and heat loss were
described previously .•* Space does not .permit a repetition of the description of
the methods in detail in this report. In brief, the water loss was measured by
having the subjects exhale through aluminum coils cooled by carbon dioxide
snow. By means of suitable valves and gas meters the subjects would inspire
room air and expire the water laden air through the collecting coils where the
water was condensed. Simultaneously, the water content of an equal volume of
room air was mea.surcd by the same method. The volume of air irrigating the
respiratory tract per unit of time Avas recorded by the gas meters. By weighing
the aluminum coils on an analytical balance before and after the collecting
of the water and simultaneously measuring the water content of the air inspired,
tin? rate of water loss from the respirator^' tract became known.

To measure the heat loss simultaneously Avith the measurement of Avater
loss from the respiratory tract, thennocouplcs Avere inserted in the aft'erent and
efferent paths of the respired air. This made it possible to learn the heat ex-
change by warming or cooling inspired air. From the Avatcr loss, heat loss from
evaporation Avas calculated. From the A'olume of carbon dioxide liberated, the
heat loss from the decomiiosition of carbonic acid Avas learned. The total rate of

AhU-il l,y thr nor-kcft'Ufr Koiinilatlim nnil th»‘ Heli.H In*illtutc for MoCIcal llo.'fcarcli.
lv»^1 for i.vibltc.uton l>.c. 12, lOl.',.

earttju'nt of Mi-,liclno, ToJanc M<.-<Jlcat School, anti the Charity HospIUiI.

?•>< % Orl< 'US'*. l-Ti.

6S

BURCH : RATES OF WATER AND HEAT LOSS FR0:M RESPIRATORY TRACT 89

heat loss from the body was measured by the ordinary clinical t 3 i)e of basal
metabolism apparatus. From these methods (see previous report^ for details) it
was possible to measure quantitatively: (1) the rate of respiration, (2) the
volume of tidal air, (3) the rate of irrigation of the respiratory tract with air,
(4) the rate of carbon dioxide liberation, (5) the rate of heat loss from carbon
dioxide liberation, (6) the rate of water loss, (7) the rate of heat loss from the
evaporation of water, (8) the temperature of the expired air, (9) tlie relative
humidity of the expired air, (1,0) the heat loss or gain by the warming or cool-
ing of inspired air, (11) the relationships of each component of heat loss from
the respiratory tract to the total heat loss, and (12) the relationship of heat
loss from the respiratory tract to total body heat loss.

The 24 subjects employed in these studies suffered from uncomplicated
right and left congestive heart failure. The etiologj’- of the failure varied;
hjqjertension, arteriosclerosis, sj’-philis, rheumatic fever, or ‘‘toxic” myocarditis
(precise nature unlmo^vn) was the cause in descending order of frequencjL
The age, sex, and color distributions are indicated by Tables I and II, All
of the patients were in Functional Class IV^ during the studies, except for Sub-
jects 1 and 2, w4iose state of cardiac function varied while under repeated
observations for several weeks. Although all of the patients were bedriddpn
because of thefr heart failure, none of them were in a state of peripheral circula-
tory collapse and none were moribund. All of them had marked dyspnea,
orthopnea, fine moist rales in the bases of the lungs, edema of tlie feet and legs,
a large liver, and the other usual symptoms and signs of congestive heart failure.
With only two exceptions the patients showed either beginning cardiac compensa-
tion or no change in the functional capacity of the heart. In the two subjects
the state of the heart failure %vas progressively becoming worse during hospital-
ization and study. AU patients were receiving treatment for congestive heart
failure. This included bed rest, low salt intake, digitalis, and diuretics, including
intravenous mercurial diuretics. Two subjects had auricular fibrillation.

The subjects were transported from Charity Hospital to the laboratory at
Tulane. They rested in the sitting position during the entire study, resting for
at least thirty minutes before any observations were begun. It required ap-
proximately thirty minutes to complete the observations. The conditions of the
environment are indicated by Tables I and II. Repeated measurements were
made on some of the subjects. All patients were dressed in a cotton hospital
type of gown and then covered from the waist down witli a col ton slieet.

During the coui’se of the study of these patients, patients with otlier disea.se
states and normal subjects were observed as controls. The results on the
normal subjects were reported previously.^ Data from the paper will be em-
ployed freely for purposes of comparison. The studies on the patients witli
other disease states will be reported in detail as a group at a later date.

RESULTS

The results are summarized by Tables I and II and Pigs. 1 and 2.

The Rate of Water Loss . — ^In a comfortable en\dronmcnt with a mean
temperature of 20.1° C. (extremes, 19.5° and 21.1°) and a mean relative humid-

no

AMERICAN HEART JOURKAI

ity of o6 per cent (extremes., 47 and 67),^ the mean rate of M-atcr loss for tlie
24 jiatients M'ith congestive heart failure was 0.944 Gm. per square meter of
.surface area per ten minutes, the extremes being 0.625 and 1.482 (Table I).
Wlien the room conditions wore changed slightly by raising tlie temperature
1.4° .0. (mean, 21.5° G. ; extremes, 21.1° and 22.2°) and lowering the relative

humitlily somvwhat (mean, 51 per cent, extremes, 44 and 57 1,'* the rate of
water lo.ss remained e.ssentially unchanged {mean, 1.0.52; extremes. 0.694 and
1.456 Gm. per square meter of .surface area per ten minutes). Under both
fuvironinental l■onditions the nunn atmo-sjdiere was eomfortahle. The .statistical
constants are shown in Tables I and 11.

Ui h>' kn**tvn :>* Ui'* ••nvlronjnfnt nt 20* C. atid tbr conifortiit)!*"'

♦ nvift.nrn* rtt ut C.

BURCH : RATES OF WATER AND HEAT LOSS PROM RESPIRATORY TRACT 91

Pis 0 The results of repeated measurements upon two patients with congesUve heart

failure studied over a period of three or more w'eeks. A and"unUs fndi-

and B on Patient 2. The various lines shown reP^’^^sent the measurements

cated. In order to use a common ordinate the true value. V, ^^as i educed or mcieaseu .

multiples of ten as indicated. ' i = respiratory volume in c.c. ^ “ Rate of total bod>

• t (V)

heat loss in calorie per square meter of surface area per ten minutes .

5 = Rate of

total loss of heat from the respiratory tract. H. in m*^calorie^i^/ten

(V X 101. — Rate of heat loss bv convection, he, from the lespiiatory tract m caioiie.^i . /lc

minutes (V x 10). .'5 = Rate of carbon dioxide Vv^y^Toi 7 = Rate of

of heat loss by convection, he, as percentage of total body heat loss x 10).

respiration, in minutes S = Dry bulb temperature of environment in “ C. . .<) =

Rate of heat loss from carbon dioxide excretion, hco=, in calorie/M.Vten minutes (V x 10).
10 = Temperature of the expired air in » n = Rate of heat loss from the excretion

of carbon dioxide as percentage of total body heat loss in calorie/M.Vten minutes (AO- 12 =
Rate of irrigation of the respiratory tract with air in llters/M.Vten minutes .y-. 13 = Rate

of heat loss by the vaporization of water, he, in calorie/M.-/ten minutes (\ x 10). Ilf —

Relative humidity of the room air in percentage 15 = Rate of heat loss by the vaporiza-
tion of ^yater as percentage of total body heat loss in ^lorie/M.Vten minutes (V). 16 =
Barometric pressure of room atmosphere in mm. Hg 1’< — P^ate of water loss in

grams/M.Vten minutes (V x 10). 18 — Rate of total heat loss from the respiratory tract

in calorie/M.Vten minutes (V x 10). 10 = Relative humidity of the expired air in per-

centage

T-Mii.r 1. Titi; roNiurioN'K ok thi; Room AT^coSI•u^;t:^; axo tuk Ratks of W.vtku and IFeat Losses Fiiom the KEsionATOiiY Tiiact of Twi'.N'TY-ONn
!*atu:,st.s With FuNo'rioxAt, (ir.Ass IV Ric.ht and Le^’ VK.vTKicuEAn Conoestive Heart Paieuke. The Patients

Rested SirriNct Qeietry in a COifFORTAUEE Koo^[ at 20.1° C.

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BURCH ; KATES OP AVATER AKD HEAT LOSS FROJI RESPIRATORY TILVCT 95

Temperature of the Expired Au*.— The mean temperature of the expired
air was 33.1° C. (extremes, 31.1 and 34.2) for the comfortable environment at
: 20° C. When the environment was changed to 21.5° C., the mean temperature
of the expired air was 33.4° C. (extremes, 32.5 and 34.8). The statistical con-
stants, are shovui in Tables I and II.

Belative Humidity of the Expired Air . — The mean relative humidity of
the expired air was 87 per cent (extremes, 82 and 94) when the patients were
in the room at 20° C. When the temperature of the room was changed to
21.5° C. the mean value increased to 88 per cent (extremes, 83 and 96). The
value of 96 per cent (Table I) is most probably an erroneous value. This was
the only such value obtained under the above room conditions. The statistical
constants are found in Tables I and II.

Bate of Irrigation of the Bespiratory Tract With Air . — In the comfortable
environment at 20° C,, the mean rate at which the respiratory tract was irri-
gated with air was 44.929 liters per square meter of body surface area per
ten minutes (extremes, 25.381 and 70.259). In the room atmosphere at 21.5° C.

, the mean rate was 48.286 liters per square meter of body surface area per ten
minutes (extremes, 37.266 and 74.238). The statistical constants are indicated
by Tables I and II.

There was a high positive correlation between the rate of water loss and
the rate of irrigation of, the respiratory tract with air, the coefficient of correla-
tion being 0.9346 ± 0.0144. The coefficient of correlation betAveen the rate of
■ irrigation of the respiratory tract to the rate of total body heat production
(oxygen consumption) Avas 0.6449 ± 0.0666.

; Bate of Heat Loss From the Bespiratory Tract . — Tlie mean rate of heal
' loss. by the vaporization of AA^ater, he, 0.553 calorie per square meter of body
' area per ten minutes (extremes, 0.286 and 0.868) Avhen the comfortable environ-
ment Avas at 20° C. and 0.617 (extreme,s, 0.407 and 0.853) Avhen the enAuron-
meiit AA^as at 21.5° C. This represented an aA’^erage of 6.55 per cent (extremes,
.3.84 and 8.99) of the total heat lost from the body and about 54.5 per cent
(extremes, 28.2 and 85.7) of the total heat lost from the respiratory tract.

The mean rate of heat loss by convection or vanning inspii’ed air, he, aa^s
0.157 calorie per square meter of body area iier ten minutes .(extreme.s, 0.108
and 0.231) at the 21.5° C. environment. This represented a mean of about 1.85
per cent (extremes, 1.26 and 2.45) of the total heat lost from the body and
about 15.5 per cent (extremes, 9 and 24.5) of the total lost from the respira-
tory tract.

The mean rate of heat loss by the decomposition of carbonic acid Avith
the expiration of carbon dioxide, hcos 0.305 calorie per square meter of
surface area per ten minutes (extremes, 0.198 and 0.440) for the comfortable
temperature at 20° C. The mean rate aa^s 0.319 calorie per square meter of
body surface per ten minutes (extremes, 0.264 and 0.419) for the room tempera-
ture of 21° C. The heat lost from the expiration of carbon dioxide represented
about 3.63 per cent (extremes, 3.32 and 4.25) of the total loss of body heat or
30.1 per cent (extremes, 19.6 and 43.4) of the total heat lost from the respira-
tory. tract.

96

AMERICAN HEART JOURNAL

The mean rate of total loss of heat from the respiratory tract -was 1.013
calories per square meter of body area per ten mimites (extremes, 0.631 and
1.830) -wlien the comfortable room temperature was 20° C. and a mean of
1.093 (range, 0.796 to 14.81) of the total heat lost from the body.

The mean I’ate of total heat loss from the body was S.20 calories per square
meter of body surface area per ten minutes (extremes, 6.56 and 10.50) when
the subjects rested in a comfortable environment at 20° C. ; the mean rate was
8.74 (extremes, 7.12 and 11.54) at a room temperature of 21° C.

Individual variations for each component of heat loss are given in detail
in Tables I and II.

Prolonged Period, of Sindg in Two Paticnis . — Two patients mth moderately
severe right and left ventricular congestive heart failure (Functional Class IV)
were studied repeatedly over a ijeriod of three to six weelcs. One patient
(Patient 1) had mj-oearditis of undetermined etiology and the other (Patient 2)
had syphilitic aortic regurgitation. Tlie first subject died two weeks after com-
pletion of the last ol)scrvalion (no autopsy o])1ained), and the other is still
living but has remained in Functional Class III. During the entire period of
study Patient 1 remained in Functional Class IV, showing onlj’' slight variations
in the degree of failure. Patient 2 returned to Functional Class III and was
in that state for the two final recordings noted in Fig. 2. Both patients were
in their most severe state of failure during the initial observations. Patient 2
had a definite exacerbation of her failure during the tenth day of observation.

Fig. 2 summarizes in detail the fluctuations in the various physiologic
phenomena recorded. It can be scon that, in the main, there arc definite varia-
tions in the rates of water and heat losses. It was not until Patient 2 reached
a fairly steady state of cardiac function (in Class III) that the observed phe-
nomena became stabilized.

DISCUSSION

It can be seen from the results and especially from Fig. 1 that the rates
of water and heat lo.ss from the respiratory tract in congestive heart failure arc
greater than normal. The.se incrca.ses over the normal are essentially proportional
and appear to conform to that which would be expected upon the basis of in-
creased rates of irrigation of the respiratory tract ■with air (dyspnea) and me-
tabolism. This fact is borne out by the percentage increases in value of the
various physiologic phenomena observed. Consult Pig. 1 for the percentage
change from the normal in patients -with congestive heart failure, A study
of Fig, 1 reveals that the increases in water and heat lost from the respiratory
tract are more the result of the dyspnea with the resultant increase in the rate
of irrigation of the respiratory U'act with air than to an increase in the rate of
metabolism as.sociated with the congestive heart failure. For example, there wa.s
an increase of 25.G ])er cent in the rale of irrigation of the respiratory tract 'with
air, 17.7 }*cr cent in the rate of water lo.s.s. 19.4 per cent in the rate of heat
loss by warming inspired air. and 9.1 per cent in the total amount of heat loss
from the res{>iratory tract. At the same time there was an increa.se of onlj' 4,8
per cent in heat l(i.<s by the excretion of carbon dioxide and 6.7 per cent increase

BURCH: RATES OP WATER AND HEAT LOSS PROM RESPIRATORY TRACT 97

in the metabolic rate. The rates of Avater loss and heat loss by convection Avhich
depend upon the rate of irrigation of the lungs with air shoAved the greatest
degree of increase over the normal, Avliile heat loss from carbon dioxide excre-
tion, dependent mainly upon tlie rate of metabolism, slioAved relatively little in-
crease over the normal. Therefore, the ventilation of the lungs and not me-
tabolism Avas largely responsible for the differences noted betAveen congestive
heart failure and the normal.

As in the normal subjects,^ there Avas a high positive correlation between
the rate of irrigation of the respiratory tract Avith air and the rate of water
loss, the coefficients of correlation being 0.914 ± 0.014 in the patients with
congestive heart failure. These findings are to be expected since the amount of
Avater vapor that might be conveyed aAA'^ay by air is dependent in a large
measure upon the amount of air available.

Since the carrying capacity of a unit volume of inspired air Avas the same
in both groups of studies, the possible causes for differences in the rates of Avater
loss betAveen the normal subjects and the patients AAuth heart failure might be
due to: (1) the presence of large amounts of free fluid in the alveoli and small
bronchioles in the patients Avith left A'-entricular failure and pulmonaiy edema
and (2) the dyspnea. All of the patients AAOth heart failure had fine moist rales
at the bases of the lungs and all had a moderate amount of dyspnea. None had
gurgling rales or Avere frothing at the mouth and none suffered Avdth severe
dyspnea, shock, and marked apprehension. Since the mean relative humidity
of the expired air Avas 88 per cent (extremes, 78 and 96.5) for the normal and
87 (extremes, 74 and 96) for the patients Avith heart failure, the same amount
of water vapor Avas added to each unit A'olume of inspired air in spite of the
dyspnea and the extra amount of free fluid in the lungs in the patients Avith
heart failure. The surface area of the pulmonary epithelium Avas probably
reduced by the accumulation of fluid in the heart failure patients ; but either
because of insufficient change in the area or because of an increase of the
vapor tension above the edema fluid, the relative humidity of the expired air ‘did
Rot change significantly from normal. The total amount of AA’^ater lost in left
ventricular congestive heart failure via the respiratory tract Avas 25.6 per cent
greater than that for the normal under comparable conditions because of the
dyspnea and the resultant rapid rate of irrigation of the respiratory tract Avith
air.. Obviously, the rate of heat loss by the vaporization of Avater follows the
same principles and arguments governing AAmter loss just described.

Under similar atmospheric conditions the temperature of the air expired
by the normal subjects Avas 33.2° C. (extremes, 31.6 and 34.2) Avhile the
temperature of the air expired by patients with congestive heart failure was
33.0° C. (extremes, 31.1 and 34.2) . As in the case of the relative humidity of
the expired air, the presence of fluid in the lungs and the dyspnea did not inter-
fere significantly with the Avarming of inspired air. The rate of heat loss by
convection Avas 27.6 per cent greater in the patients Avith congestive heart
failure, hoAv.ever. This increase Avas due to the greater rate of irrigation of the
respiratory tract with air.

98

A:MERICA^' HEART JOtTRXAE

Since the rate of metabolism was only 6,7 per cent greater in the patients
with congestive heart failure, and since the excretion of carbon dioxide is mainly
dependent upon the rate of metaboblism, the heat loss fronr tile decomposition
of carbonic acid in the lungs resulted only in a relatively slight increase in the
rate of heat loss by cai'bon dioxide excretion. Therefore, the greater rate of
heat loss (D.l per cent) in congestive heart failure was due to an increase in
the rate of heat loss by vaporization and eonveetion.'

The total body heat loss was not determined directly but was estimated by,
first, measuring tlie rate of heat production from the rate of oxygen consumption
and, second, assuming that the subject resting for sixty minutes in the com-
fortable room was in a state of thermal equilibrium with the environment. It is
obvious that such an estimation of total body heat loss is subject to error.
This may explain the finding that there was an increase above the normal of
9.1 per cent in heat loss from the lungs with only a 6.7 per eenl increase in total
l)ody heat loss, a difference of 2.4 per cent. It is more likely, however, that this
difference is due in large part to the dj'spnea with tlie associated rapid rale of
ventilation of the respiratory tract Avith air and the resultant increase in heat
loss by A'aiiorization of Avater and convection of heat. Obviously, such a dis-
crepancy could exist for only a short period of time, as during a paroxysm of
dyspnea, or tliere AA’ould result an associated decrease in body heat. Tlie nature
of the above studies rendered it impossible to evaluate such plmnomena.

SUMMARY

A study of the rates of AA^ater and lieat loss from the res])iratory tract of
24 resting sitting ijatients Avith right and left ventricular co’ngestiA’e heart failure
(Fimctional Class IV) and living in tlie subtropical climate of Noav Orleans
shoAved the following Avhen the room atmosphere aa’Os comfortable (tcmpei’ature,
20.1® C. ; relath'e humidity, 56 per cent) :

1. The mean rale of Avater loss from the res])iratory tract aatis 0.944 Gm.
per square meter of body area per ten minutes (extremes, 0.625 and 1.4S2).
When the room temperature aa'Os increased from 20.1° C. to 21.5° C., the mean
rate of loss A\-as c.ssentially unchanged (mean, 1.052; extremes, 0.694 and 1.456).

2. The mean temperature of the expired air AA*as 33.1° C. (extremes, 31.1
and 34.2). The A'alues AA’Cre 33.4° G. (extremes, 32.5 and 34.8) Avhen the room
temperature AA'as increa.sed to 21.5° C.

3. The mean i‘elatiA*e humidity of the expired air Avas 87 per cent (ex-
tremes. 82 and 94). The value became 88 per cent (extremes, S3 and 96) Avhen
the room temperature AA*as changed to 21.5° C.

4. The mean rate of irrigation of the respiratory tract Avith air Avas 44.929
liters per square meter of body area per ton minutes (extremes, 25.381 mid
70.259). When the room temperature AA-as increased to 21.5° C. these values
became 48.286 liters (extremes. 37.266 and 74.238),

5. There was a high correlation betAveen the rates of Avater loss and irriga-

tion of the respiratory tract AA-jtb air. the coefiieient of correlation being 0.934 f
0.0144. ‘ ■

BURCH : RATES 0P‘ WATER AND HEAT LOSS FROM RESPIRATORY TRACT 99

6. The TtiGRH rate of lieat loss from the respiratory tract bj'" the vaporization
of water, he, was 0.553 calorie per square meter of body area per ten minutes
(extremes, 0.286 and 0.868). Tlie values became 0.617 (extremes, 0.407 and
0.853 when the room temperature ^vas raised to 21.5° C. This represented 6.55
per cent (extremes, 3.84 and 8.99) of the total heat lost from the body and 54.5
per cent (extremes, 28.2 and 85.7) of the total heat lost from the respiratory
tract.

7. The mean rate of heat loss bj'' convection, he, or warming inspired air
was 0.157 calorie per square meter of bodj’’ area per ten minutes (extremes, 0.091
and 0.248). The values became 0.157 (extremes, 0.108 and 0.231) when the
room temperature was changed to 21.5° C. This represented a mean of 1.85
per cent (extremes, 1.26 and 2.45) of the total heat lost from the body and 15.5
per cent (extremes, 9 and 24.5) of the total lost from the respiratoiy tract.

8. The mean rate of heat loss by the decomposition of carbonic acid and
excretion of carbon dioxide, hco 2 , was 0.305 calorie per square meter of body
area per ten minutes (extremes, 0.198 and 0.440). The value became 0.319
(extremes, 0.264 and 0.419) when the room temperature was increased to 21.5°
C. This represented 3.63 per cent (extremes, 3.32 and 4.25) of the total heat
lost from the body and 30.1 jiei cent (extremes, 19.6 and 43.4) of the total
heat lost from the respiratory tract.

9. The mean total rate of heat loss from tlie respiratory tract was 1.013
calorie per square meter of body area per ten minutes (extremes 0.631 and
1.830). The values became 1.093 (extremes, 0.796 and 1.503) when the room
temperature wms increased to 21.5° C. This represented 12.04 per cent (ex-
tremes, 8.78 and 14.81) of the total heat lost from the body.

10. The rates of water and heat loss from the respiratory tract of patients
with left and right ventricular congestive heart failure (Function Class lY)
were definitely greater than the rates observed under similar conditions in 107
normal subjects. These increases were due in a large measure to the dyspnea
and associated increased rate of irrigation of the respiratoiy tract with air.
The extra amount of edema fluid in the lungs apparently influenced the results
verj^ little. A theoretical discussion of the principles concerned is presented.

An. appreciation for the heen intere.st and significant technical assistance of Mr. G.
orgavi is expressed.

REFERENCES

Burch, G. E.: The Bate of Water and- Heat Loss From the Eespiratorj- Tract of Normal
Subjects in a Subtropical Climate, Ai'ch. Int. Med. 76 : 315-.327,_1945.

Burch, G. E.: The Bate of Water Loss From the Skin of Patients in Congestive Heart
Failure in a Subtropical Climate, Am. J. M. Sc. 211: 181-18S, 1946. , , „

Calabresi, M., and Bocchini, G. : Water Metabolism in the Lungs in Decompensated Heart

Disease, Clin. med. ital. 68: 519-533, 1937. -r. • ^ m .p -w

Burch, G. E.: A Study of Water and Heat Loss From the Bespiratory Tract of ilan.
Methods- I A Gravimetric Method for the Measurement of the Bate of Water
Loss, li, A Quantitative Method for tlie Measurement of the Bate of Heat Loss,

Arch. Int. Med. 76: 308-314, 1945. ^ ^ ^ i

.Nomenclature and Criteria for Diagnosis of Diseases of the Heart by the New York
Heart Association, New York, 1942.

WOLFF-PARKINSON-WHITE SYNDRO]\IE

A CLiNiCAii Study With Report of Nike Cases

Captain Daitd Litt.mann, j\LC., and SLvjor Herji.sn TARNO^^^sR, i\I.C.

Army of the United States

T he number of cases reported during tlie past few years would indicate that
the syndrome of a “short PR ipterval with a prolonged, aberrant QRS com-
plex” occurs much more frequently than has hitherto been realized. The cri-
teria for diagnosis have been modified and the theories which have been advanced
in explanation of the findings liai’c become more numerous and involved.

Tliough the anomaly had been reported previously, “■ Wolff, Parkinson,
and White-^ were the first to present a group of cases that illustrated all of the
common features. Tlieir original article suggested that increased vagus tone
was responsible for the short P-R interval and QRS prolongation. This ap-
peared to be eonfii-med in those instances in which exercise or the administration
of atropine produced a nonnal eleetrocardiograpliic pattern. As lias been
pointed out this theory implies a paradoxical effect of vagus tone with a si-
multaneous exercise of two diametrically opposed influences, one accelerating
conduction between auricles and ventricles uith shortening of the P-R inter-
val, the other retarding conduction through the bundle of His giving I’ise to the
lengthening and distortion of the QRS complex.

Hunter, Papp, and Parkinson^^ later suggested that the electrocardiographic
findings could be explained as being the result of a “fusion beat,” on the basis
of a “double rhythm” in which the auricular impulse fuses with a heat which
arises in one bundle branch. They postulated two ccntci-s bcai-ing a constant
relationship. The hjqiothcsis explains many of the findings but it is difficult to
accept when other .simpler mechanisms ba.sed on anatomic findings and experi-
mental demonstrations arc available. Also, as has been demonstrated, pi'cmaturc
auricular beats may be followed by the usual distorted QRS complex.""

The most satisfactory explanation to date was initially advanced by Holz-
mann and Sche& in 1932’" and by Wolfeidh and Wood in 1933, and is based
on the hypothc.sis of an accc.ssoiy pathway of A-Y conduction with ventricular
asynchronism as a re.sult of the pmnaturc .stimulation of one ventricle.

The existence of accessory neuromuscular connections between the auricles
and ventricles was demonstrated by Kent in 1914'" and by Glomsel and Glomset
in 1940.' In 1943, Wood, Wolferth, and Gcckeler,"- through serial microscopic
sections of the aurieuloventrieular groove, were able to identify a “Bundle of
Kent” m the heart of an individual who, during life, .showed the anomaly of a
short P-R interval and a prolonged QRS complex with iiaroxy.smal tachycardia.

n.-r-iv. .1 ft.r i.iit.Hi-.-itif.n uci. loin.

100

LITTMANJSr AND TARNOWER : WOLPF-PARKINSON- WHITE SYNDROME 101

The interesting experimental work of Bntteiworth and Poindexter^’ ^ has
added further weiglit to the theoiy that an accessory pathway is responsible for
the phenomena observed in this sjuidrome. By means of an electrical amplifier
the impulses from the auricle were conducted to one ventricle before they were
conducted to this ventricle normally through the auriculoventricular conduction
system. This produced typical electrocardiographic tracings Avith a short P-R
interval and QRS prolongation. Reversal of the electrical stimulus from ven-
tricle to auricle resulted in auricular tachycardia.

the use of atropine. BYT, diminished vagus tone.

The simple hypothesis of an accessory A-V pathway has always left much
to be desired in the explanation of the Wolff-Parldnson-mite syndrome. With
the study of “fusion beats’" by Butterworth and Poindexter^ we have an im-
portant contribution to the better understanding of the mechanisms iiivolved.
Their work supports the supposition that an auricular impulse may travel doAvn

102

a:mericax hExVRt .iourxal

both the A-V bundle and an accessory pathway and result in a ‘“iusion beat.”
The QRS configuration is clotcrniined by the degree of fusion wliicli in turn
is dependent upon the speed of conduetioi\ in each channel and the relative prox-
imity of these channels to the initiating impulse. These authors clemon.stratcil
that the ventricle can be stimulated tlmough the normal conduction system ami
by a second ventricular stimulus only durijig the .short period (approximately
0.08 second) lU'ior to the time the normal QRS complex would ordinarily ap-
pear.

It has been repeatedly pointed out that the Wolff-I’arkinson-White .syn-
drome occurs most commonly in young healthy adults. IMany authors reporting
instances in Avhich myocardial damage Avas very likely or possibly present have
made it a ]mint to disregard or minimize that feature. In more recent years a
few articles have appeared in which the ]>resence of myocardial ]iathology is
.stressed.®’ In reviewing our own cases and those in the literature wc have
been struck Avith the fact that no eases have been re 2 :)orted in infants, that a
number of cases shoAving the Wolff-Parkinson-White syndrome have subsequently
lost all evidence of it,’®* and that many published electrocardiograms indicate
obAUous myocardial disease. Though Ave arc at a loss to explain the connection,
it Avould appear that the 2 :)resenco of disease is more than a coincidence. Hunter
and his associates'^ thoroughly rcvicAved the literature and found that, of ninety
cases reported, eighteen had evidence of cardiac disease. They remarked that
the syndrome luidoubtedly could be produced by heart disease but pointed out
that the presence of a short P-R interval Avith QRS distortion in no Avay in-
fluenced the prognosis. They noted that the syndrome Avas found associated
Anth mitral steno.sis, hypertension, aortic insufficiency (.syjfiiilitic and rheu-
matic), coronary thrombosis, and thyrotoxicosis. The oldest patient reported
Avas 62 years of age, AVolferth and Wood'® reported the syndrome in a child of
14 Avho had a histoiy of recurring j)aroxysmal tachycardia from the age of 2
years.

We are reporting nine ca.scs that illustrate .some of the valuations encoun-
tered. They came to our attention during a period of one year in which ap-
lu'oximately 3.600 electrocardiograms were revicAved.

RKPORT OF C-A.^KS

0.\sr. 1. — .A. SO-your-wW ^o\^VH‘r eumo into tiic tiosjiitnl on Dec. 'J, 10-54, ticiMUisc of

^hortncss of hreatli and a ‘ ‘ tlutlorinu” seiij-atiou in flio ••lic'.-t. Tlioro Iiail Itfon two j)r<'viouH
cpi.'iodcs of d.v.-:pnea and tadiwardia williin tin* prefoding lliroo ^Tar^^, oafli Ia^ting nix to i-ovon
days. Althnugli tliorc Avas a Iiistory of .“oine pliortnC'>s of hrcalli .-inco oldldliood, tliis np-
liarmtly did not intorfcro with his I'listoinar}' artivif it’.*!. Tho family and pa.st history acre
nom-ontrihutory.

Tho heart was not onlarued. Xo iminmir!! wore present. The heart late was 120 at the
wrist and approximately l.'!U at the ajtex. The rhythm was totally irregular. The lungs were
clear. .\ soft ma.“.s, the si/e of a ha/elniit, wa.*! noted in the left lobe of the thyroi*!. I lie
examination wa- otherwise iinniud.

A’itn! rapacity, cirenlation time. Wood, urine, and x-ray studies of the heart were all
norninl. The basal metabolism w;i5 -10,

LITTMANK AND TARNOWER ; WOLFF-PARKINSON- WHITE SYNDROME

103

The patient was digitalized, and by the follomng morning the rhythm was regular
with a rate of 86 per minute. ' The sounds were of good quality and no murmurs or thrills
were noted. Digitalis was omitted the second day and, except when used experimentally
later, was not again employed. During the two months that he was observed there were no
other episodes of tachycardia or arrhjdhmia an'd no other cardiac symptoms.

Comment . — Tliis was a ease wliieli demonstrated auricular fibrillation with
pei-sistence of the abnormal ventricular pattern indicating that the distribution
was largely via the accessoiy pathway. It strongly resembles Case 1 of Levine
and Beeson 's^^ .series which was interpreted as ventricular tachycardia. During
■ both spontaneous and induced (quinidine) reversion to normal distribution, To
and T 3 became shaiqily inverted resembling in appearance the curves seen in myo-
cardial disease. Yarying degrees of fusion could be produced with quinidine.

-I

II.

;..:Y ■ VY:

: :i.\J

. \ ••
•! f

• • • I *’• • •

■vii ^ ;.\i

' -

A*’

2.— Case 1. A, nbrillat^ t g^ 3 .ig deviation. jB,

and 340 per minute. Duration of. QKS aPP'oxi'uateiy rnixture of normal and

This eraph, made following- cessation of tachjcard.a temons^rr^^^ ^

aberrant complexes. The normal conmlexes (Beats 1 am ^ and a QRS duration of O.Ofi

and Beat 4 in Lead III) have a P-R -rCand Ts. The aberrant complexes have a

second with an upright Ti and sh^rplj imerted t.^an^ denionstrate eft axis

P-R interval of 0.06 second and a abnormal beats are identical. C. All of the

deviation. The P-S' intervals of the tiormal jj-|-.pj^j.]^inson-Wliite syndrome. Measurenients
complexes are typical of those seen the U oul ^ abnormal beats in B .

and contour of the complexes are essentiallj

Case 2 26 vear-old white soldier came into the hospital on JIarch 11, 194o, uith

» eomplaint of “rapid Jating of tl.e Iicait.” Dmrag the preceding three jears he had
been subject to fairly frequent episodes of typical paroxysmal taobycard.a
no treat^nt OTien seen by the admitting officer, the pulse was found to be bet, een 1 0
and 180 per miuLe, but by Hie time an electrocardiogram was made the rate was well wnthlu

normal limits.

104

AMERICAN’ HEART JOURNAL

Physical examination revealed a healthy looking young man who was completely com-
fortable. The heart was entirely normal on examination. X-ray films of the chest showed
no evidence of cardiac enlargement. The vital capacity, circulation time, and all cardiac
function tests were normal. "iMiile under observation tlie patient had no cardiac complaints
nor did he experience any further attacks of tachycardia.

mc }}{. — Altliough DO jiaro.xysuijil lachycardiu was recorded, this appears
typical ease o£ tlic 'Wolft-Parkinson-White .syndrome. Normal eoiidiic-
Ul be obtained with qninidine, and intennediate forms were recorded
)pine and alroitinc witii exorcise.

3- — A 3” -year- old wliito .‘.ohlier wiis admitted on .Tan. 2, 1915, vdtli complaints of
and abdominal pain. Tlicro wore no cardiac .«ymptom.».

LITTMANN AND TARNOWER : WOLPF-PARKINSON-WHITE SYNDROME 105

Physical examination ■s\as entirelj’’ unremarkable with the exception of some evidence
of moderate weight loss and dehydration. The heart was within normal limits. An x-ray film
of the heart was normal. All caidiae function studie.s were normal. Stool examination re-
\ealed trophozoites of JEii-dctinocha histolytica and the diagnosis of amebic dysentery was
made. Before beginning treatment with emetine, an electrocardiogram was made and found
to be abnormal (Fig. oa).

During the period of hospitalization this patient exhibited no paroxysmal tachycardia
and had no cardiac complaint of any character.

II.

III.

IVP.

Wip- A o A nvifoSno/i nn nflmi'ssion P-R intervals 0.08 second. QRS duration 0.12

recond Slurrlne ot'tlfo Siitlal stroke of the QBS "’m-J fnS?SS' 0 fi

a “'a f iSteat’?!! anfBeTf ‘SSI

demonstrated in a end t? nnd rpnresent varying degrees or lusion. J- "ft n-iu seeona.

0 10 tsennnei i ^lintncip 71 Made after intravenous atropine and exercise.

second. -Axis normal. Ti diphasic.. „„tp uDrielit P^t (inverted in

Except for the rate this curve is very similar to B. However, nore upngnr 1^3 unveiieu

other tracings).

Comment. This patient never had paroxysmal tachj^cardia or any. other

cardiac complaint. Although varying degrees of ‘‘fusion” could lie produced
with the administration of quinidine and atropine, tiie electrocardiographic
pattern could not he brought hack to normal.

J06

AMEfJFCAX Hri:.\RT JOURXAL

r.'.sj: •}. — A ‘JJ'-year-dlil soldier eaiiie info the hospital on Dec. «. 1044, with a eompl.aitit
of uttnek.s of rapid hetirt action uceompanie<l by .«hortne.s? of breath. He had been rcceivino-
luiii.'-yphUitie therapy. Bci-ause of a positive spinal fluid Wasserinann, he was transferred to
an appropriate installation for definitive treatment, but was retunied to the original station
because of tin abnormal electrocardiogram.

Physical examination, was not remarkable. The heart was not enlarged, the rate was
moderate, the rhythm wa.s regular, and the .sounds were good. Xo murmurs or thrill.s were
noted. The lungs wore clear and re.soiiant throughout, and the reflexc.s were noruuil. All
!a])nratory .studies and cardiac function tests were within normal limits.

, -t, Ot'tained on iidmi.ssion. I’-R, O.OS .second. QltS, 0.14 second. Left

iixiH uovUitmn. IS, Taken after the ailnjfnlstralion of riui’nkline (24 grains Jn tliree hour.c), IMi
to njca>«re but are probably not appreciably altered. There is a chanKc
the appeanmee of n larce l\z and a f?maU "and diminution in the dept!)
li t r higher, T- is lower, and is inverted. A laryo T 4 is noted, C. Becorded following'
the luiminislralion of atropine.

riio pafi('nf continued to receive antisvphilitie tlierupv whih' on flu" caniiac ward. Hix
or sevc 7 i hour.v after one .such treatnieiit lu' eomjilained of a fluttering sensation in the che.st
arid of breathlessness. This attack I'crsisted for about one hour and toward its conclusion
it wits noted that the piil.'-c was irregular.

During tlie two ritontfis tliat this sotdier was under oiiservation there were no instances
01 di'liuite paroxvsuud tachycardia and no cardiac symptoms.

(.■imunnt . — The tachycardia ijt

thi.s cfi.se is rather slow to be eoti.sidered

pamxysuial in charttetcr. Furthcnnt>rc, the short P-K.
perstst.s. T!ie .signinc.-itice of this is not ciotir.

wide QHS relationship

Of ccmsiderahle

lowing sintis pause.s.

iutcrc.st is the
This is itikcn

;ip{>i'arance of noriiial QR.S eoinpk'.xes fol-
io indicjilc that sitice 1ho.se venlrictdar eoiii-

uttmakj, ASD TAKAWEB: WOEFF-PARKINSOS-WHITE SFVDRn

siadro::me in ?

piexes were the resiilf nf 7'T>T>, t . . .10 (

A-V node, transmission distal from »f the

not mvolTo the accessoiy pathway. ^ ‘ ^eshion and did

nAc » 7 T » if t —

I , J .- — ,

frequent atfacitf 0^1^ tl.T'''*';- '’'■''® >‘»-'pitalfaoa on May •>■, .

mp.<l I.on,t net, on during t,,e „.ooi-o tW;,. because of

I;

t‘:

•i '■•

l-i

lOS

AMERICAX HEABT JOURNAL

first attack came on suddenly three years earlier. Greater physical activity encountered in
the Army was apparently responsible for the increasingr frequency of the episodes. There
were no other cardiac symptoms and no complaints of any kind between attacks of tachy-
cardia.

Pliysical examination was entirely unremarkable with the c.xception of a soft systolic
murmur which was best heard over the apex. The pulse was slow and regular. The heart
was not enlarged. The lungs were clear. All the laboratory procedures and cardiac function
tests were found to be normal.

Following a long period of observation, wo were able to obtain a tracing during n
paroxysm of tachycardia. This was controlled by breath holding.

Kim T. — Ca.‘!e .'5. A, Obtained on admission, K-R, 0.10 second. QRS. 0.12 second. Axis
normal. R Obtained during a paroxysm of tncliycardln. Rate 210. Rhytiim probably parox-
ysmal nodal tacliycardia. F waves are not idcntiflabic. QRS, 0.06 second. Axis essentially un-
altered. Eleetrlc.al altcmans noted, C, Made following administration of (ptlnltUne (24
rrains In tliree liour.s), I’-U. O.it .^eci nd. OltS. O.OS second. Sligiit left axis deviation.
T Waves lowered, rounded, prolonged, and notched duo to qulnidino effect.

Commeni. — TJie di;5gRo.si.s' in Ihi.s ca.se ivas ob.scia-e bccanso accurate niea.sure-
incnt was dinicult. Addilionidly, the nxi.s was norjual. Tlie u.sc of qiiinidinc
procliiocd ciinngcs wliich ^ycre definile though not .spectacular, TJie record ob-
tained during tlie iiaro.xy.sni of tacliycardia confirni.s the diagnosis. liathcr
marked elocti-ieal filternan.s apjieared during the tachycardia.

C.vsn G. — A a(i-year-ohl soklier eaine into the hospital on June 12, tvith the com-

plaint that his heart ocra<-ifmany ‘‘ .-•kippeil a heal." On rare occasions, ever since chihl-
Ikkk!, he also is said to have had .short periods of nipid heart action. Tlie only other com-
piiuat referable to tlie heart was tliai of ily.-.pnea on moderate exertion. During a previous
laopitaiization a diajyno-is of heart b!o‘-k was raid to have been m.ade.

LITTJMANN AND T^VENOWEB: WOEFF-PARKINSON-WHITE SYNDROME . 109

On physical examination the heart was not enlarged, the rate was moderate, the rhj^thm
was regular, and the sounds were good. ’No murmurs or thrills were noted. A rare extra-
systole was observed. X-ray films of the chest were normal and all cardiac function tests
and laboratory procedures were within normal limits.

During the period of hospitalization there were no episodes of tachycardia and no
cardiac symptoms.

Fie:. 8. — Case G. A, Recorded on admission. P-R, 0.08 second. QRS, 0.16 second. Initial
deflection of R wave is slurred. Axis normal. B, Ventiucular extrasystoles are present.' Pre-
mature beats were never observed except following exercise and were always associated with
depression or inversion of tlie T waves in the limb leads. G, This tracing was obtained fol-
lowing vigorous exercise. Rate, 11 G. P-R, 0.10 second. QRS, 0.10 second. T waves sharply
inverted In all limb leads and .S-T segments slightly depressed. There is diminution in the
size of all weaves in Lead IV.

Comment . — This case is of interest in that ventricular premature beats
were recorded. They' occurred following slight exercise and were abolished
during greater activity.

The same case presented a phenomenon ivhich to us is vuthout adequate ex-
planation. Electrocardiograms made following brisk exercise always demon-
strated inversion of the T waves in the limb leads and diminution in height
of all the waves in Lead IV. There was also a slight increase in the P-R inter-
val and a shortening of the duration of the QRS complex.

Case 7. — A. 28-year-olcl wliite soldier entered the hospital complaining of a generally tired-
out and run-down feeling. The family and past history were noncontributory. Approximately
six years earlier, he was examined for life insurance and lij-pertension was noted. He tired
rather easily on moderate effort and suffered from occasional occipital lieadaches. Tliere was
AO dyspnea on exertion nor precordial distress and no edema of the extremities was ever noted.

no

AilERICAX ITEAUT JOURXAI.

Pliysical cxnniination was not roinarkalile. The heart was not onlargei'l, the rate was
moderate, tlie rhythm was regular, and the sounds were of good quality. Xo murmurs or
thrills were noted. The blood i)re.=sure was 150/92. X-ray films of the heart demonstrated
no enlargement or distortion. The lungs were normal. The serology was negative and all
other laboratory findings were normal. The cardiac function tests were normal.

During bis hospitalization the patient did not have any tachycardia nor were there any
other complaints referable to the heart.

FiR. 9. — Case 7. .V, Hecor<toil on mlmission. I'-K, 0.10 sccoml. IJUS. 0.14 sceom).

.axi.s deviation. TJie T wave.s are inverted in Fead.^ I and IV, and ui>riKlit in la>ads 11 and IH.
/; Tlds iracinj; was oltlaincd sevcnil lunns alter llial .=lio\sn in .1, and iind*T identical eii-

vated. lA-ad IV i.« unelianired. J), Thi.< tracinc was made approMinately one liour after tin
adnilril.«tration of .i.T Krain.c of quinidine. P-K. 0.1S> si-cond. '■tUt'. jt.lO .'■oeoiid.

■Jlljtht rinlit axi.s deviation with a small Hi and prominent S,. The T «ave.s are ail tarf..
and rounded. T, i.s uprm-iit. Tr and Tj are .=Uan>ly Inverted. QHS, has acquired a deel S
wave while the hemht of the K wave has dia-rea.sed. This traelnf,' strongly re.--eml)!e.« that
iititalned in Case t bv .similar means (Fiir. 3. O-

Cnvimcnt . — This ]iatieiit is of eoiisitloi'ahle interest hteaiise ol the marked
alterations in llio appearanee of the venlrienlar eoinponeiU wliieh oeeiirred
.spoilt aneou.sly ami under unvai’ving eirenmstatiees. This ehange eannot he
explained on the basis of altering degrees of fusion iieeatise the intervals
and tile QHS duration renmin eonsltmt ami unehanged. The only .satisfaetory
explanation whieh ean .snpjtoil tluvse findings is that of multipU aeee.s,sory path-
vvay.s.’* Under .sueh cireiunstanee.s. variation in the nunihor anti 'or eomhinalions
of sueh ehnnnels aeting over a given interval eouhi efiVetively alt<*r the distrihn-

LITTSIANN AND TARNO^^^i;R: WOLFF-PARKINSON- WHITE SYNDROME

111

tion of the impulse and, with it, the character of the ventricular complex. The
factors tending to influence the selection of abnormal pathways are quite beyond
our knowledge at the present time. . However, they may be susceptible to experi-
mental analysis similar to that employed by Butterworth and Poindexter.^

Administration of 83 grains of quinidine over a period of two hours pro-
duced characteristic alteration in the appearance of the tracing with reversion
to physiologic conduction.

A

Fig. 10. — Case S. A, Obtained on admission. P-R, 0.08 second. QRS 0.14 second. B, Re-
corded following moderate exercise. Note marked change in the T waves and in the RS-T seg-
ments. There is also a shift of the axis toward the left. G, Obtained following the intravenous
administra'.ion ot atropine and subsequent exercise. All of the T waves are now inverted
The duration of the QRS complex has been dimini-shed by approximately 0.02 second witli-
out a comparable increase in the P-R interval. The axis has rotated toward the right.

Case 8. — A 26-yoar-old white soldier came into the hospital on Dec. 11, 1945,, complain-
ing of restlessness and rapid, irregular heart action. This occurred suddenly following a
brisk run of some 50 yards. The admitting physician described a grossly irregular rhythm
and noted a pulse deficit. An electrocardiogram was not made unitl the following morning
at which time the arrhj’thmia had disappeared. The tracing demonstrated a normal rhythm
with a configuration characteristic of the Wolff -Parldnson-'Udiite sjm drome.

The attack for which the patient entered the, hospital was his first. The history was
otherwise noncontributory. The physical examination revealed only a soft systolic apical
murmur. All of the routine laboratory tests, cardiac function tests, and chest x-rays were
normal.

112

AJilEniCAN HEART JOURNTAI.

The use of quinidine did not alter the tracing significantly but exercise and exercise with
atropine resulted in interesting changes.

During his hospitalization the patient had no further attacks of tachycardia and did
not have any cardiac complaints.

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Comment . — The variations in the axis and in the T waves are probably the
result of A^arying combinations of the sevei'al aberrant conduction pathways
apparently present in this case. The shortening of the duration of the QRS
eomiflex Avithout a like increase in the P-R interval, liotAmver, is Avithout ade-
quate explanation.

rever.sod tlielr cUvections.

LITTMANN AKD TAENOWER : WOLFP-PARKESTSON-WHITE SYNDROME 113,

Case 9. — 20;year-old white man was admitted to the hospital on Dec. 18, 1945,
with tlie complaint of rapid and irregular heart action. There was a history of two similar
attacks, ^oth following effort, during the preceding ten years. The historj' was not othemdse
remarkable.

Physical examination revealed the presence of what' was apparently auricular fibrillation.
The lieart was not otherwise unusual and no other abnormalities were observed. An electro-
cardiogram demonstrated what was either parox 3 'smal ventricular tachycardia with consider-
able irregularity or auricular fibrillation witli bundle brancli block and an exceedingly rapid
ventricular rate.

The attack stopped spontaneously during the night and on tlie following morning the
cardiac rate was moderate and the rhjdhm regular. An electrocardiogi-am at this time demon-
strated a characteristic short P-E, long QES relationship.

All of the customary laboratory studies were normal. X-ray of the chest and cardiac
function tests were all within normal limits.

It was not possible to produce anj’- significant alterations of the electrocardiogram by the
use of exercise, atropine, or quinidine. However, a rather unusual electrocardiographic
phenomenon was observed in tliis patient after he had changed his position from right lateral
to supine. Several seconds after the change was completed there was an abrupt shift in axis
and all of the T waves reversed their direction. That this was not due purely to the anatomic
change in position is apparent when it is recalled that there was a delay of several seconds
before the electrical change occurred.

Comment . — The tachycardia in this ease is probably of the same type as that
found in Case 1. It disappeared spontaneously. The immediate cause for the
gross changes noted with alteration of anatomic position is not apparent. How-
ever, the meclianism is doubtless similar to that postulated in Cases 6, 7, and S.

DISCUSSION

Several details of this condition merit somewhat further discussion and
theory. It has usually been considered that the attacks of paroxysmal tachy-
cardia so frequently associated with this syndrome are the result of impulse
re-entry through the anomalous A-V bundle. Since most of the tachycardias
recorded are of the supraventricular type with a nonnal QRS complex it is prob-
able that the original impulse in such instances travels from the auricle down
tlie normal A-V pathway and returns to the auricle through the aberrant chan-
nel. The inability of the ‘‘Kent bundle” to transmit retrograde impulses would
explain the freedom from paroxysmal tachj^cardia noted in approximately 25
per cent of the reported cases.

In reviewing those cases which were considered to be ventricular tachy-
cardia^^’ it is felt that some of the electrocardiograms shown might have been
interpreted as auricular fibrillation with a prolonged, distorted QRS sunilar to
Cases 1 and 9 herein reported. In order to explain the wide, bizarre QRS com-
plex, it is necessary to postulate that the path of distribution is largely through
the accessory bundle. The cases of true ventricular tachycardia probabl}^ arise
in the lower portion of the aberrant pathwa.y.

An investigation of this subject by Rosenbaum and his co-workers^‘ recently
appeared in the Journal. We were interested to find that their deductions,
arrived at through careful studies witli unipolar leads from the e.sophagus, pre-
cordium, and other parts of the thorax, closely resemble the experimental con-

114

A:Mr,RICAN KEART JOURXAE

elusions of Buttcnvortli and Poindexter.^' They do not employ the tenn “fusion
beats'' but conclude that “impulses" i)ass from the auricles to the ventricles
not only by way of the atrioventricular node and Ilis bundle but by “one or
more additional channels." Tliey also su{;<,mst tliat tliese pathways may be
present but not functioning. Tbe.se conclusions a]>pear valid when applied to
those cases showing a mixture of abnormal and phy.siologic complexes (Case 1)
and where the abnoiaual complexes vary in apj'iearance ( Case 4) .

If the presence of one or more conduction pathways is conceded, the
phannaeologie action ,of rpiinidiiie aiid atropine become apparent. Quinidine
by its dcprc.ssant action on ectopic tissue is thought to delay conduction in the
aberrant system thus poi-mitting tlic impulse to t)rogrc.S's down the normal path-
way (Pig. 1, C). Atropine, on the other hand, by dimini.shing or aboli.shing
7iormal or incrca.sed vagus control ovoi* the A-V conduction system makes the
normal pathway the more favorable one and allows the im]>ul.se to take that
route in preference to the acee.ssoiy jiathway (Fig. 1, D). One may liken the
two (or more) pathways to comjmting electrical circuits having dilTcrent and
\miying resistances, with the impulse mosfl.v or wholly traversing the one with
the least impedance.

Since the phannaeologie action of quinidine and atropine in this condition
is apparently complementary, the one interfering witli nlmonnal conduction
and the other enhancing ])liysiologie conduelion. the two drugs were used
simnllaneously in those cases not altered by either drug separately. However, it
was noted that whore quinidine alone did Jiot indneo normal conduction the
addition of the other drug resulted in no further elmmxe. The dose of quinidine
required to produce physiologic conduction varied from 6 giuins an hour for two
or three doses to 33 grains in two hours (Case 7). Atropine in intravenous doses
np to %f) grain and atrojunc witli exercise were also effective to a lesser degree.
We were unable to obtain satisfactory results with digitalis even though large
doses were employed. In Case 1 the rhythm changed from anricnlar fibrillation
to normal either because of or in spite of digitalis.

It is interesting to note that in tlio.se cases where ]>iiysiologic tracings were
obtained following the use of quinidine (Cases 1, 2, and 5) the histoiy indicated
a faii'ly recent origin or paroxysmal tachycardia. In Case 7 changes were
secured by similar means but this patient bad no cardiac complaints. One maj'
speculate that electrocardiographic reversal by pharmacologic means is more
likely to occur in those eases where the aberrant mechanism is not one of long
standing. In borderline cases it maj' be jiossible to einjiloj’ quinidine as a diag-
nostic test.

Tlie relationship of myocardial disease to the Woltf-Parkinson-AVhite
sjTidrome is, in our opinion, the major unexplained issue. It is generally ad-
mitted that the syndrome may be produced occasionally by heart disease. Case
1, which showed deep inversion of T„ and T- when the conduction was physiologic
suggests that myocardial disease may have had some part. Tliis factor should
not be lost sight of, and the nature of the cause, if it can be determined, should
always be carefully considered in making a prognosis. A few attractive theories

LITTMANN and TARNOWER: ‘WOLPF-PARKINSON- WHITE SYNDROME 115

have been advanced, but no conclusive evidence has been presented. Pox^ has
suggested that a circulatoiy difficulty of the A-V node due to coronaiy sclerosis
may sufficiently depress its functional actiwty to permit an already present
ectopic mechanism to take over some of the conducting functions. Other
inflammatoiy, toxic or degenerative processes could conceivably have a similar
eifect. It is our opinion that this phase of the problem has not been sufficiently
emphasized or investigated.

SraijMARY AND CONCLUSION

1. Nine patients who sho^ved the Wolff-Parldnson-White Syndrome are pre-
sented and a few of the variations encountered are discussed.

2. The various theories advanced in the explanation of the pathogenesis
are referred to and an evaluation of their merits is attempted. In our opinion
the most acceptable explanation is that which assumes the presence of one and
frequently several accessorj^ conduction pathways wliich result in ‘‘fusion
beats. ’ ’

3. The influence of quinidine, atropine, and exercise on the “short P-E,
long and aberrant QRS” is discussed. In borderline cases these changes may
be employed as a diagnostic test.

4. The relationship of myocardial disease to the Wolff-Parldnson-White
sjTidrome is discussed. Several of the patients reported in this paper had
sj^^stemic disease and two showed definite electrocardiographic abnormalities
during periods of normal conduction. '

REFERENCES

1. Buttenvorth, J. S,, and Poinde.xter, C. A.: Short P-E Interval Associated With a Pro-

longed QES Complex. A Clinical and Experimental Study, Arch. Int. Med. 69:
1437, 1942.

2. Butterwortli, J. S.: The Experimental Production of the SjTidrome of Apparent

Bundle Branch Block With Short P-E Interval, J. Clin. Investigation 20: 458,
1941. ,

3. ' Butterworth, J. S., ,and Poindexter, C. A.: Fusion Beats and Their Eelation to the

SjTidrome of Sfiort P-E Interval Associated With a Prolonged QES Complex, Am.
Heaet j. 28: 149, 1944.

4. Fox, T. T. : Aberrant Atrioventricular Conduction in a Case Shoving a Short P-E

Interval and an Abnormal but Prolonged QES Complex, Am. J. M. Sc. 209: 199,
1945.

5. Fox, T. T., Travell, J., and Molofsky, L.: Action of Digitalis on Conduction in the

Syndrome of Short P-E Inten’al and Prolonged QES Complex, Arch. Int. Med. 71:
206, 1943.

6. Franke, H., and Vetter,- E.: Beitrage zur Pathogenese der Herzstrom Kurven mit

Verkurzter, Vorhof Kammer-Distanz und mit Verbreiterter Anfongschvankung, Arch.
Kreislaufforsch. 11: 283, 1943.

7. Glomset, D. J., and Glomset, A. T.: A Morphologic Study of the Cardiac Conduction

System in Ungulates, Dog, and Man, Aji. Heart J. 20: 389, 1940.

8. Granpera, E., and Govia, J.: Nueva Teoria Patogenica del Sindrome de Wolff,

Parkinson y White, Vida Nueva 52: 272, 1943.

9. Hamburger, W. W.: Bundle Branch Block. Pour Cases of Intraventricular Block

Showing Some Interesting and Unusual Clinical Features, M. Clin. North America
13: 343, 1929.

10. Holzmann, M., and Scherf, D.: Ueber Elektrocardiogramme mit verkurzter Vorhof-

, Hammer-Distanz und positiven P-Zacken, Ztschr. f. klin. Med. 121: 404, 1932.

11. Hunter, A., Papp, C., and Parkinson, J.: The Syndrome of Short P-E Interval, Ap-

parent Bundle Branch Block and Associated Paroxysmal Tachycardia, Brit. Heart
J. 2: 107, 1940.

116

a:merican heart journal

12. a. Keut, A. F. S.: Proceedings of Physiol. Soc., ISTov. 12, J. Physiol., 1892.

b. Idem: The Structure of the Cardiac Tissues at the Auriculoventricular Junction, J.

Physiol. 47: 17, 1913.

c. Idem: Observations on the Auriculoventricular Junction of the Mammalian Heart,

Quart. J. Exper. Physiol. 7: 193, 1913.

d. Idem: The Eight Lateral Auriculov’entricular Junction of the Heart, J. Physiol. 48:

22, 1914.

e. Idem: A Conducting Path Between the Eight Auricle and External lYall of the

Eight Ventricle in the Heart of a Mammal, J. Ph 3 *siol. 48; 57, 1914.

f. Idem: - Illustrations of the Eight Lateral Auriculoventricular Junction in the Heart,

J. Phj'siol. 48: 63, 1914.

13. Levine, S. A., and Beeson, P. B. : The AVolff-Parldnson-White Sj’ndrome, IVith Paroxysms

of Ventricular Tachj'cardia, Am. Heart J. 22: 401, 1941.

14. Mahaim, I.: Le Si'ndromc de 'WoUT-Parkinson-lVhite et sa Pathogenic, Helvet. nied.

acta. 8: 483, 1941.

15. Movitt, H- H-‘ Some Observations on the Syndrome of Short P-E Interval With

Long QES, Am. Heart .1. 29: 1, 1945.

16. Palatucci, O. A., and Knighton, J. E.: Short P-E Interval Associated With Prolonga-

tion of QES Complex; A Clinical Study' Demonstrating Interesting Variations,
Ann. Int. IMed. 21: 58, 1944.

17. Kosenbaum, P. F., Hecht, H. H., Wilson, F. K., and Johnston, F. D.: The Potential

Variations of the Thorax and the Esophagus in Anomalous Atrioventricular Excita-
tion CWoltf -Parkinson- White Syndrome) Am. Heart J. 29: 281, 1945.

18. Wilson, F. N.; A Case in IVhich the Vagus Influenced the Form of the Ventricular

Complex of the Electrocardiogram, Arch. Int. Med. 16: 1008, 1915.

19. Wolfei-th, C. C., and Wood, P. C. : The Mechanism of Production of Short P-E Intervals

and Prolonged QES Complexes in Patients With Presumably Undamaged Hearts;
Hj'pothesis of an Accessory Pathway of Auriculoventricular Condition (Bundle of
Kent) Am. He.art J. 8; 297, 1933.

20. Wolferth, C. C., and Wood, F. C.; Further Observation on the Mechanism of the Produc-

tion of a Short P-E Interval in Association With Prolongation of tlie QES Complex,
Am. Heart J. 22: 450, 1941.

21. Wolff, L., Parkinson, J., and White, P. D.; Bundle Branch Block With the Short P-E

Interval in Healthy- Young People Prone to Paroxysmal Tachycardia, Am. Heart
J. 5: 685, 1930.

22. Wood, F. C., Wolferth, C. C., and Geckeler, G. D.; Histologic Demonstration of Ac-

cessory- Muscular Connections Between Auricle and Ventricle in a Case of Short
P-B Interval and Prolonged QES Complex, Am. Heart J. 25: 454, 1943.

Clinical Reports

TRANSIENT VENTRICULAR FIBRILLATION

Report op a Case With Spontaneous Recovery

Walter T. Zimdahl, M.E,, and Frank T. Fulton, M.D.

Providence, R. I.

I T HAS been fairly ^yell recognized in recent years that cardiac sjmcope may
result from transient ventricular standstill or ventricular fibilUation, Ven-
ti'icular fibrillation in man is often a terminal event in various forms of cardiac
failure, particularly sudden occlusion of the coronaiy vessels^’ - It has been
shoAvn bj^ several investigators, particularly Schwartz and Jezer,® that
ventricular fibrillation may occur as a transient disorder from wliich the patient
may recover. Until the studies of these authors, little was known of the clinical
manifestations of tliis disorder.

Schwartz^ pointed out that the periods of unconsciousness in patients with
auficuloventricular dissociation are associated with transient seizures of ven-
tricular fibrillation much more eommonlj’’ than had been suspected. He called
attention to the fact that the clinical diagnosis of transient ventiicular fibrillation
ina}’- be suspected in such patients if, preceding a period of unconsciousness, the
heart rate has been noted to increase above the usual basic rate. Schwartz and
Jezer® also presented a patient in which certain premonitory disturbances pre-
ceded a transient seizure of ventricular fibrillation. One such distiu’banee con-
sisted of alternate premature beats of the ventricles, which increased the basic
ventricular rate. These were followed siiortl^y by irregular periods of recurring
groups of aberrant ventricular oscillations, of which only the fir-st few could be
heard at the apical region of the heart or felt at the radial pulse. Borg and
Johnson'^ presented a ease of ventricular standstill which had had an arrhytlimia
similar to that described as a prefibrillatory mechanism. They .suggested that
the clinical diagnosis of this disturbance is probably impossible without electro-
cardiographic records.

. Most of the patients described by these authors had A-Y heart block in
sortie form. The number of such cases which have been described is compara-
tively small and we feel it worth while to report another ease.

CASE REPORT

J. H., a 5G-year-old white man, was admitted to the Ehode Island Hospital, May 8,
1915, heeause of "convulsions.” Except for scarlet fever in childhood there was no history
of previous illness.

From the Heart Station of the Rhode Island Hospital, Providence, R. I.

Received for publication June 24, 1945.

117

118

AMERICAN IIEAET JOURNAL

Two weeks before admission lie did not feel well and rested for one day. Tliree davs
before admission he developed an illness characterized by chills without cough, which liis
physician diagnosed as ''pneumonia/' and for which he was given full doses of sulfadiazine.
Ho progressed favorably and felt well. Pour hours before Jidmission he was found on the
floor of his bathroom. He was very c 3 ’anotic and had generalized twitchings from which he
recovered in a short time. Three additional .seizures occurred before he reached the hospital.

Soon after admission the patient suddenly became extremely cj'anotic, apneic, and
pulseless. Oxj'gen and coraminc were administered immediatelj'. Because of the absence of
pulse and apical sounds and because of the marked cj'unosi.s, ventricular standstill was con-
sidered to bo the cause of the sj’ncope. He wa.s given 0.1 Gm. of Metrazol .subcutaneously
overj* five minutes, for a total of O.G Gm. The blood pressure at this time was not obtainable.
The patient graduallj* lost his cyanosis, became flushed, and then regained his normal color.

Examination between attacks revealed that the patient was a well-developed, rather obese
man who was clear!}' oriented. The blood pres.sure was 320/90; the rectal temperature, 101.0°
P. ; respirations, 30; and the pulse rate, 320 per minute. Tlio pulse, initiall}' irregular,
graduall}' became regular. The lungs revealed diminution of breath sounds at the left base
and a few crepitant rales. The heart was enlarged to the loft and no murmurs were audible.
The peripheral vessels were sclerotic.

Electrocardiogram taken at this time (Fig. 1, Column 1) showed a ventricular rate of
80 per minute with a regular sinus rhythm and right bundle branch block.

A few minutes after the tracing was taken the patient suddenlj- became pale, closed
his ej'es, and manifested general tAvitching, following which his eyes opened and he appeared
motionless. At this time no pulse or apical heart sound could be heard. His respirations in-
creased to 40. The patient was unconscious and his face was purplish. The inspiratory
phase became almost double the expiratorj' xflm.cc and the brenthing was noted to bo stertorous.
Ho again developed a short convulsive seizure which involved the whole body during which
his ej'Cs rolled irregularly to the left .and upward. Two minutes later the rc.spirations stopped;
ho became intensely cj’anotic and appeared lifeless. This episode lasted for a period of one
minute. Spontaneous rcvii’al Avas associated As-ith the return of tlic heartbeat and respirations.

Upon regaining full consciousness ho was incoherent and confused but Avithin a few
minutes became rational and asked, “Did I Iuia'c another?"

During this period of syncope avIucIi lasted about five minutes, he was incontinent
of urine.

AVithin a period of eight hours, the patient had fifteen such attacks, each lasting approxi-
mately tAvo to six minutes. An electrocardiogram taken during one of these attacks is .«hoAvn
in Pig. 2. After tho fifteenth seizure the patient remained asymptomatic and rested com-
fortably.

PolloAAung liis last seizure, tho patient Avas giA'en 0.2 Gm. of quinidine sulfate orallj'
every four hours. This was continued for ten daj's folloAving Avhich the dosage Avas gradually
reduced to 0.2 Gm. every tAvelve hours. On the tAA'eatj'-third day, the drug was discontinued.
After he had been free of all sj-mptoms for thirtj'-seven daj's, he was discharged from the
hospital.

ELECTROCARDIOGR AMS

Fig. 1, Column 2 , shows the electrocardiogram taken Maj^ 9, 1945. It shows
sinus rhythm, a rate of 76, A-V conduction time of 0.20 second, and right bundle
branch block. There is marked slurring of the QRS complexes. The T waves are
upright in Leads I and II, slightly inverted in Lead III, and diphasic in CF^.

A record taken May 11, tlu’ee daj's later (Colunui 3 ), shows T-wave changes
in all leads. These waves are flattened in Lead I, smaller in Lead II, upright
and small in Lead III, and inverted in GF^. The marked slurrmg of the QRS
complex has disappeared.

ZIMDAHL AND FULTON: TRANSIENT VENTRICULAR FIBRILLATION 119

A record taken May 15, four days later (Colimm 4 ), shows further changes.
These changes suggest that the patient had marked coronary artery disease and
that an acute myocardial infarction had initiated his sjuieopal attacks. Further
serial records confirmed this diagno.sis.

Pig. 1. — Serial electrocardiograms taken on the day of admission between syncopal sei-
zures, on the following day, three days after admission, and seven days after, respectively.
They showed normal sinus rhythm, riglit bundle branch block, and T-wave changes. Further
records proved the diagnosis of acute myocardial infarction.

Fig. 2 shows a continuous electrocardiogram (Lead II) taken during and at
the end of a typical seizure of transient ventricular fibrillation. The tracing
was interrupted only twice, once in the third strip and once in the bottom strip,
because the patient had a convulsion and the string could not be controlled. In
the second strip the rhytiim is quite regular and is similar to the tracing re-
ported by Gertz and his co-workers® as representing ''ventricular flutter.”

Fig. 3 shows a tracing (Lead II) during the same seizure. Strips 1 and 2
show a rapid ventricular rate which varied and oscillations which differ in
shape and in amplitude. At this time the patient was extremely cyanotic and
pulseless. His eyeballs rolled upward and involuntary urination occurred. The
patient was apneic during this period and appeared lifeless. Strip 3 shows a
slowing of the ventricular rate to 260 and sudden cessation of the attack with
a short postundulatory pause and the establishment of an idioventricular rhythm.
With the onset of ventricular contractions, a clonic convulsion threw the string
out of the field for a few seconds. As the ventricles commenced to beat the

ZUrDAHL AND FULTON: TRANSIENT VENTRICULAR FIBRILLATION 121

Vfrr <} A continuous record taken on Lead II showing: Hie end of the syncopal a,ttack.

rin f' sho^4 «ie aKit end of the transient ventricular fibrillation followed by a post-,
idSlatorvTause aifd t^ of an intermediary idioventricular rhythm In Strip 5 there

nenr“^rmarLmXxes fn which the P-R interval is increased to 0.30 second. In Strip
fXw”n^ the sS^entdcular ectopic beat the P-B interval is 0.24 second and at the end
the strip it is 0.20 second.

122

AMERICAN HEART JOURNAL

pulse became perceptible, tlie cyanosis cleared, and the patient appeared flushed.
Gasping respirations began and as the patient regained consciousness he began to
breathe regularly. Strip 4 shows idioventricular rhythm. The upright com-
plexes occur regularly and appear to represent an idioventricular rhythm from
a different focus. It is possible that these complexes may represent lower nodal
rhythm with the P wave following the QRS complex. However, the notching
probably is due to slurring of the QRS complex and goes to make up the QRS
interval. In the next strip similar complexes appear with occasional ones which
resemble the patient's '‘normal” complexes.

The P-R intervals of these beats are much inci’eased, the duration being
0.30 second. The duration returns to normal in Strip 6 following two ven-
tricular ectopic beats. The P-R interval following the second ventricular ectopic
beat in Strip 6 is 0.24 .second. Normal rhytlnu is established at the end of
Strip 6.

DISCUSSION

Most of tile eases* reported have been associated ivith some form of heart
block or advanced coronary arteriosclerosis. Davis and Sprague^® observe that
the poor prognosis in patients with disease of the biuidle tissues suggests that
coordinated ventricular action is dependent upon activity of the nodal centers
situated in the bundle tissue. It wmuld seem that with complete depression of
these tissues, ventricular action, save ventricular tachycardia or ventricular
flbriUation, is impossible. This fact, together with the common association of
heart block and ventricular fibrillation, they hold as evidence in favor of their
hypothesis.

Of interest was the mode of spontaneous recovery of the heart observed in
this patient. Schwartz^ reported two distinct modes of recovery from ventricular
fibrillation. In one type, the fibrillation ceased promptly and was followed by a
postundulatory pause varying from 0.8 second to 1 second. The basic ventricular
rhytlim did not appear for several seconds after this, and it was preceded by an
idioventricular rhythm. The second type of recovery was also sudden, but was
not followed by a postundulatory pause ; the idioventricular rhjdhm arose fi'om
the last of the waves terminating the ventricular fibrillation. Fig. 3, Strip 3,
shows the cessation of the ventiacular fibrillation followed by a postundulatory
pause and the resumption of an idioventricular rhythm.

Davis and Sprague^® discuss the mechanism of the cessation of attaelvs in
their case. They say, "It is apparent that the depression of the bundle tissues
and Purkinje system that we hold responsible for the onset of fibrillation, re-
covered sufficiently to permit transmission. If this recovery took place in the
presence of circus movements in the ventricular muscle, these circus movements
would theoretically be brought to a close by the first excitation arising from the
node and distributing through the Purkinje system to the musculature. This
would destroy any responsive gap and result in a general state of refractoriness
from which the ventricle would recover and permit the continuity of rhythmic
control from the nodal center. As long as the nodal center and Purldnje fibers

ZIMDAHL AND FULTON: TRANSIENT VENTRICULAR FIBRILLATION

123

remained cxcitalile, tins rhythm would continue. With the appearance of further
depression, fibrillation might be precipitated again.

■ iiletrazol was given to tiiis patient at first because it was thought that the
syncopal attaclcs were due to ventricular' standstill. This therapy has been sug-
gested by Lueth.^^ When the nature of the disturbance was observed in the
electrocardiogram, this drug was discontinued and quinidine sulfate was started
by oral dosage.

Levine'^^ reported the effect of quinidine in inhibiting ventricular fibrillation.
Dock® reported a case of recurrent attacks of syncope oeeiirring over a period of
eighteen months due presumably to ventricular fibrillation. Subsequent
quinidine medication prevented these attacks. Gertz and his co-workers® re-
ported a ease iii which the patient had aliout twenty syncopal attacks. Quinidine
sulfate was ineffective lij' mouth because of nausea and vomiting. After her
last attack the patient lapsed into coma and intravenous quinidine sulfate and
other measures were without avail. Davis and Sprague, in their paper, discuss
the possible action of quinidine in initiating ventricular fibrillation.

We feel sure that the attacks which are described in this paper stopped
spontaneously and not as a result of the quinidine therapjL However the
quinidine sulfate was continued for several weeks. Since his discharge the
patient has been followed in tlie Outpatient Department and has remained free
of all s.'smiptoms.

SUMMARY

1. A patient with coronary artery disease and intraventricular block who
suffered from fifteen seizures of unconsciousness during a period of eight hours
with spontaneous recovery is reported.

2. The syncopal attacks were shown to be the result of transient ventricular
fibrillation.

3. Spontaneous revival from a seizure of ventricular fibrillation was ushered
in by the appearance in the elect i-ocardiogram, of a postundulatory pause
followed by idioventricular rhythm, and ventricular ectopic beats and finally bj^
normal sinus rhytlun.

REFERENCES

1. Fulton, Frank T.: Eeinarks Upon the Manner of Death hi Coronary Thrombosis, Am.

Heart J. 1: 138, 192.5.

2. Miller, Henry: Ventricular Fibrillation as the Mechanism of Sudden Death in Patients

With Coronary Occlusion, New England J. Med. 221: 564-569, 1939.

3. Schwartz, S. P.: Studies on Transient Ventricular Fibrillation. IV. Observations on

the Clinical and Graphic Manifestations Following the Revival of the Heart From
Transient Ventricular Fibrillation, Am. ,T. M. Sc. 192: 808, 1936.

4. Schwartz S. P. : Transient Ventricular Fibrillation: _A Study of the Electrocardiograms

Obtained From a Patient Witli Auriculoventricular Dissociation and Eecurrent
Sjmcopal Attacks, Arch. Int. Med. 49: 282, 1932.

5. Schwartz S P.: Studies in Transient Ventricular Fibrillation. III. The Prefibrillatory

Meciianism During Established Auriculo-Ventricular Dissociation, Am. J. M. Sc. 192:

6. Schwartz and Jezer, A.: Transient Ventricular Fibrillation: .The Clinical and

Electrocardiographic Manifestations of the Syncopal Seizures in a Patient With
Auriculoventricular Dissociation, Arch. Int. Med. 50: 4^, 1932.

7. Borg, J. F., and Johnson, C. E.: Cardiac Syncope, Am. Heart J. 13: 88, 1937.

124

AMERICAN heart JOURNAL

8. Gertz, G., Kaplan, H. A., Kaplan, L., and Weinstein, W.: Cardiac Syncope Due to

Paroxysms of Ventricular Flutter and Fibrillation, and Asystole in a Patient With
Varying Degrees of A-V Block and Intraventricular Block: Report of a Case,
Am. Heart J, 16: 225, 1938.

9. Dock, W.: Transitory Ventricular Fibrillation as a Cause of Syncope and Its Prevention

by Qninidino Sulfate, Am. Heart J. 4; 109, 1928.

10. Davis, D., Sprague, H. B. : A^ontrieular Fibrillation: Its Relation to Heart Block. Re-

port of a Case in Which Syncopal Attacks and Death Occurred in tlie Course of
Quinidine Therapy, Am. Heart J. 4: 559, 1929.

11. Lueth, H. C. : The Use of Metrazol in Complete Heart Block With Adams-Stokes Syn-

drome, Am. Heart J. 16: 555, 1938.

12. Levine, H. D.: Effect of Quinidine Sulfate in Inhibiting Ventricular Fibrillation, Arch.

Int. Med. 49: 808, 1932.

Abstracts and Reviews

Selected Abstracts

Allen, Arthur W.: Thromhosis and Embolism. Bull. Isew York Acad. Med. 22: 169 (April)

1916.

Considei'ing the results of ligation of the femoral veins in 816 patients, Allen believes
that thrombectomy and bilateral suijerticial femoral vein interruption is a safe and satis-
factory method of treating early thrombophlebitis. It is a reliable method of preventing
pulmonary embolism after eliiiical chart, signs, or symptoms, show evidence of phlebothrom-
bosis. Prophylactic bilateral supcrfici.al femoral vein interruption is a safe and harmless
j»rocoduro and prevents postoperative thronibosis and embolism. It is particularly suitable
in the older age group of i)atients. Common femoral vein interruption is not recommended
in spite of one f.'ital embolus, occurring in the author’s series, from the profunda femoris
vein after superficial femoral interruption. .Serious sequelae can occur under certain cir-
cumstances from common femoral vein occlu.sion. The technical difficulties far outweigh
any added protection to the patient. Dicoumarol in small doses appears to be safe and
effective in selected patients as a pi'eventive against thrombosis and embolism. It is useful
in conjunction with femoral vein inlerruj)tion after thrombosis occurs. Careful laboratory
ob,servations on the plasma prothrombin time preoperatively and after dicoumarol admin-
istration are imperative for the safety of the patient when this drug is used. Naide.

Samuels, S. S.: Peripheral Arterial Diseases. Post-Grad. M. J. 22: 22 (Jan.) 1946.

This is a review of some of the diagnostic and therapeutic procedures used in arterio-
sclerosis and thromboangiitis oblitcrams. The method of management of gangrene in these
two disea.se.? i.s de.scribed in detail. The indications and level of amputation are discussed.

Naide.

Garber, N.: The Cure of Varicose Veins. South African kl. J, 20: 67 (Feb. 9) 1946.

The local and general distuibances incident to the injection of sclcro.?ing solutions
with varicosity of the long and .short saphenous veins are reviewed. The high percentage
of recurrence and dangers attending ligation rvith retrograde instillation of sclerosing media
are pointed out. The author has done 384 multiple resection operations with minor post-
operative disability, no recurrence, and no mortality even in the aged. The operation lasts
from one and one-half to four and one-half hours in each leg depending upon the size,
number,* and accessibility of the veins (presence or absence of obesity) and whether the
ve.?sels are intimately adherent to the ovcilying skin as a result of mild but persistent
chronic cellulitis. From fifteen to thirty divisions are made under local anesthesia. The
incisions lie. across the course of the long saphenous and are from % to %(j inch in length.
Despite the lengthy course of the operative procedure, shock is absent. Most patients are
back at work mthin three weeks if both legs have been subjected to operation. The oper-
ation is recommended by the author as the method of choice for permanent obliteration of
varicosities. Naide.

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Gold, H., Otto, H. L., Modell, W., and Halpem, S, L,: Behavior of Synthetic Esters of
'strophanthidin, the Acetate, Propionate, Butyrate, and Benzoate, in Man. J. Phar-
macol. & Exper. Therap. 86; 301, 1946.

Patients -with auricular fibrillation were studied to test the effects of the acetate,
propionate, butyrate, and benzoate esters of strophanthidin. The heart rates -were counted
at the apex before and after the oral and intravenous administration of the drugs. All
-were fully effective in about thirty minutes or less when given intravenously as judged by
the decline in heart rate. The oral administration of six times the effective intravenous
dose of the acetate ester was not productive of a significant decline in heart rate. The
benzoate was most effective by mouth in that only two and one-half times the intravenous
dose was required to obtain a reduction in heart rate equivalent to that observed following
its intravenous administration. Its full effect was observed in about two to three hours,
and its duration of action was nearly eight hours. Orally, the propionate and butyrate
esters were intermediate in their efScacy. Toxic effects were observed with all prepara-
tions and were the same as with digitalis. Friedlakd.

Adlercrantz, E.: On the Neurocirculatory Syndrome (Neiirocirculatory Asthenia) in
Soldiers. Acta. med. Scandinav. 123: 219, 1946.

Sixty-eight Finnish soldiers with neiirocirculatory asthenia were observed. The ma-
jority were between 20 to 29 years of age. Sixty-one were from the laboring group in
contradistinction to Lewis's observation in World War I, namely that the majority of his
patients left “sedentary occupations to enter the armj% The most frequent symptoms were
previous “heart trouble,” dizziness, and headache. Sweats, tremor, tachycardia, and
cyanosis of the hands and feet were common. Cardiac hypertrophy as judged by x-ray
examinations was present in seven patients. Only occasional patients had systolic mur-
murs or extrasystoles. The resting systolic pressure was 145 mm. Hg or more in 54 pa-
tients, whereas the diastolic pressure was 90 mm. Hg or less in 44 patients. Orthostatic
tachycardia and lu'potension were observed in 26. The electrocardiogram disclosed left
ventricular preponderance in five patients and riglit ventricular preponderance in nine.
Three patients had low or flat T waves in Leads I, II, and HI which became higher or
upright after exercise. Friedland.

Teilum, G.: Pathogenetic Studies on Lupus Erythematosus Disserainatus and Belated Dis-
eases. Acta. med. Scandinav. 123: 126, 1946.

A pathologic study of two patients with arteriolitis granulomatosa allergica is pre-
sented and certain features common to this disease and to lupus erythematosus dissemi-
natus, rheumatic fever, and periarteritis nodosa are pointed out. It is suggested that al-
though the etiological agents responsible for these diseases may differ, their pathology is
indicative of a common pathogenesis. A state of allergy is assumed to constitute the basis
for the similarities in tissue changes, the ultimate histopathology being related to the
etiological agent and the intensity and extent of tissue reaction induced by the agent.

Freedlakd.

Apperly, F. L., and Cary, M. K.: The Belation of Arterial Pulse Pressure to Arteriovenous
Oxygen Difference, Especially in Arterial Hypertension. Am. J. M. Sc. 211: 467, 1946.

In a previous paper the authors showed that the arteriovenous oxygen difference in
an extremity bears a reciprocal relationship to the product of the pulse pressure times the
pulse rate. In this paper, the authors show that hypertensive patients as a group tend to
have higher arterial pulse pressures and lower arteriovenous oxj^gen differences in an ex-
tremity. Assuming that the cardiac output in a InTiertensive patient differs little from
that of the normal individual, the data would indicate that the blood flow to an extremity
is greater in the hypertensive patient than in the nornal, and that there is, therefore, a
greater proportion of blood flow to muscular areas than to the viscera in hypertensive
patients. Friedland.

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127

Straus, E.., Dominguez, R., and Merliss, E.: Slowly Progressive Occlusive Thrombosis of

the Abdominal Portion of the Aorta. Am. J. M. Sc. 211: 421 (April) 1946.

Three cases of slowly progressive occlusive thrombosis of the abdominal portion of
the aorta are presented. The disease is usually secondary to a severe ulcerative arterio-
sclerosis of the arterial wall, but may follow an embolism to the bifurcation of the aorta,
or more rarely, thrombosis of the pelvic arteries after irradiation. Its mean autopsy inci-
dence is 0.12 per cent. The characteristics of this syndrome that permit differentiation
from other forms of aortic occlusion are: insidious onset; protracted course; usually, but
not always, absence of gangrene; absence of pulses in both lower extremities; intermittent
claudication; and the appearance of arterial hypertension or of signs of visceral infarction
years after the onset of claudication in the legs. Natoe.

Eanstrom, S,: Amyloidosis Myocardii. Acta. med. Scandinav. 123: 111 (No. 2) 1946.

Three cases of ' 'primary’’ cardiac amyloidosis are reported and the thirty cases in
the literature are reviewed. The only fairly constant clinical findings were rapid sedimen-
tation rate's, thought to be the result of hyperglobulinemia; and a slight or moderate hypo-
tension. Low voltage in the electrocardiogram and signs of myocardial insufficiency some-
times occurred. The heart was frequently enlarged, but its gross appearance in one of the
author’s case's was normal except for hj^tertrophy. Usually there was a greenish yellow
coloration and a semiopaque sheen wlien inA'olvement of the myocardium was' severe and
diffuse. Microscopically there might be diffuse or spotty interstitial deposits, though amyloid
was never found actuallj^ within the muscle fibers themselves. Subepicardial, subendo-
cardial, and Amlvular deposition Avas sometimes seen, the mitral A'ahm was involved in one
of the author ’s cases. Another tjqoe of deposition was amyloidosis of the smaller coronary
artery branches, in which the media and intima were almost entirely replaced by 'amyloid
and surrounded by a relatively normal adAmntitia. No .definite cause for the amyloid was
found in any of the three cases reported by the author. Sayen.

G-ladnikoff, H.: The Eoentgenological Picture of the Coarctation of the Aorta and Its

Ana-tomical Basis. Acta, radiol. 27: 8 (No. 1) 1946.

■ The author correlates the roentgenologic picture with the operative findings in three
cases of coarctation of the aorta which were repaired by Crafoord. He emphasizes that
the leftward convexity in the upper mediastinum was the dilated left subclavian artery
although it had sometimes been mistaken for the aortic knob. In all three cases the
coarcted area laj’’ at the angle of juncture of the subclavian artery and the aortic arch
or 3 to 5 cm. below it, but was drawn within the mediastinal shadow. Below the depres-
sion in the left mediastinal border the thoracic aorta could be seen, although not clearl 3 %
The aortic knob in the anteroposterior and the arch in the left anterior oblique views were
poorly seen in spite of hypertension which was expected to increase visibility. This was
explained by the shortening effects of low pressure in the aorta below the coarctation, by
contraction of the adjacent aortic wall, and by the fact that the aorta was pulled inward,
downward, and posteriorly by the shortening of the ductus botalli. The poor roentgenologic
visualization is believed to be due to the effect of coarctation on aortic length and posi-
tion. Hence, the disappearance of the shadow of the aortic arch in the x-ray is by no
means pathognomic of coarctation and can occur in any condition that causes shortening
of the aorta, such as congenital hypoplasia. Sayen.

SaArilahti, M.: On the Normal and Pathological PQ Time of the Electrocardiogram. Acta.

med. Scandinav. 123: 252 (No. 3) 1946.

Prom statistics based on 872 cases of all ages the author concludes that the length of
the P-Q interval is not directly related to the heart rate and that it remains very constant
, m any particular healthy individual except for a gradual increase Arith age in childhood

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and adolescence. The upper limits of normal for the younger age groups in the series were
0.15 second helow the age of 5 years, 0.17 second between 5 and 10 years, and 0.20 second
after the age of 15 years. In fever, the standing posture, and after exercise, the P-Q
interval often shortened; but this was not proportionate to the increased heart rate in
such states and not infrequently occurred when the rate remained relatively constant.

Sayen.

Bang, J.: A Peculiar Conduction Disturbance Persisting Latently After Recovery Prom

Complete Heart Block and Disclosed Only by Electrocardiography Pollowlng Exercise.

Acta. med. Scandinav. 123: 551 (No. 6) 1946.

The author reports the case of a 15-year-old boy who developed complete heart block
three weeks after a streptococcal tonsillitis and was subject to attacks of syncope asso-
ciated with complete pallor and mild spasms. The heart rate during block was 40 per
minute; the blood pressure was 90/80, and the sedimentation rate was 56 mm. per hour.
Leucocytosis was present and antistreptolysin titers were significantly elevated. Recovery
was gradual; a two-to-one heart block was present on the seventh day, and partial block
was recorded on the ninth da}’' after onset. The P-R interval was markedly prolonged for
thirteen days, and on discharge from the hospital it was still as high as 0.22 second.

The patient was re-examined one year later and the abnormal P-R interval, which
was still present,* was the only significant finding. After violent exercise, a marked ar-
rhythmia occurred, consisting of short runs of six or seven rapid beats, and a steadily
increasing P-R interval which reached 0.30 second, after w’hich there was a slight pause,
W’hich may have represented a dropped beat, and the rate decreased sharply. The next
several beats w’cre at a slow tempo with a P-R interval of 0.17 second. This cycle "was
repeated several times, and, after a lapse of about twenty minutes, although the rate was
regular, the P-R interval was noted to be 0.30 second, diminishing only gradually to 0.23
second. Re-examination the following year showed the identical picture, although the
patient felt quite well and led an active life throughout the period of examination and the
intervals between. Sayen.

Magnasson, P.; Auricular Standstill. Acta med. Scandinav. 123: 519 (No. 6) 1946.

Three new cases are added to the thirty-one collected from the literature. The criteria
were a regular ventricular rate and no auricular deflections in any limb or precordial lead.
The commonest causes of the disorder appeared to be digitalis or quinidine toxicitj’. The
authors emphasize the necessity of frequent electrocardiograms in patients who are receiv-
ing large doses of digitalis with normal rhythm or patients witli auricular fibrillation wlio
regain normal rhythm, since there are no diagnostic clinical symptoms of auricular stand-
still and since in animals this condition is frequently a precursor of ventricular standstill.

Sayen.

Lindqvist, T., and Soderstrom, N.: An Hnusual Electrocardiographic Manifestation of

Intra-Auricular Dissociation in a Pair of Identical Twins. Acta med. Scandinav. 123:

(No. 1) 1946.

Electrocardiographic studies were made in a pair of 42-year-old identical twins with
absolute arrhythmias. They were found to have a totally irregular ventricular rate but
with P waves preceding all complexes. The P-R intervals varied from 0.23 to 0.5 second.
Rare periods of complete atrioventricular dissociation occurred. Most of the P waves in
limb leads were double, the two peaks separated by 0;08 to 0.1 second. The second (usually
inverted) component of these P waves w’as simultaneous with the intrinsic auricular de-
flection in esophageal leads, while the first component was largest in a precordial lead near
the sternum in the third right intercostal space. They were thought to be, respectively,
left and right auricular in origin and their separateness was attributed to delayed inter-

SELECTED ABSTRACTS

129

{luricular conduction. With increased heart rates small irregular f waves appeared in one
case, in addition to the double P waves. Administration of % mg. of atropine sulfate
caused the base line to show coarse flutterlike waves, every other one being accompanied
by a P wave. The authors believe that the bizarre mechanism was caused by a localized
area of constant flbrillation, probably in the right auricle, surrounded by a ring of refrac-
tory muscle transmitting a limited number of impulses to which the remaining muscle of
the right and left auricles responded usually, and the ventricles always, with a totally
irregular rhythm. Sayex.

Leq.uieme, J., and Denoiin, H.: Circulatory Changes Following the Injection of Hypertonic
Saline Solutions. Application to the Study of Angina Pectoris. Arch. d. mal. du
coeur. 38: 231 (Sept.-Oct.) 1945.

Observations were made on the effect of intravenous injections of hypertonic saline
solution in patients who had coronarj’' disease. Forty patients were studied, all of whom
presented a typical history of angina of effort. The technique involved recording the elec-
trocardiogi'am from the limb leads before, immediately after, and live minutes after the
rapid intravenous injection of 40 c.c. of 20 per cent saline solution.

The procedure was well tolerated. All patients noted a sensation of warmth result-
ing from the injection. Six patients had anginal pain and, in two instances, the pain was
severe. In 38 of the 40 patients, the heart rate was accelerated. In 14 patients, the elec-
trocardiogram showed transient S-T interval deviation which was most conspicuous in
‘Leads II and III. In 12 patients, the T waves became flattened in Leads I and II. In 14
patients, the injection produced no significant change in the electrocardiogram. It is note-
■worthy that in the latter group, most of the patients had abnormal electrocardiograms
before the test.

In normal subjects and in cardiac patients without coronary disease, the injection
produced tachycardia and occasionally some flattening of the T waves, but there have been
no instances of S-T interval deviation. The effect of intravenous hypertonic saline on the
electrocardiogram of patients who have coronary disease is attributed to the resultant
increase in work of the heart. The procedure is recommended as a substitute for the
exercise test in the diagnosis of angina pectoris. Laplace.

Gillman, T., and Gillman, J.: The Value of Speransky’s Method of Spinal Pumping in the
Treatment of Rheumatic Fever and Rheumatoid Arthritis. Am. J. M. Sc. 211: 448
, (April) 1946. • ^

' The method of spinal pumping first described by Speransky, in 1935, was utilized by
these authors in the treatment of 70 patients suffering from acute, subacute, or chronic
forms of rheumatism with joint involvement. All the patients, with three exceptions, were
, adults. In all but two instances, 10 Gm. of sodium salicylate in divided doses were admin-
istered orally or rectally twenty-four hours before pumping and for twenty-four to forty-
eight hours after pumping. The actual "pumping" consists of withdrawal into the barrel
of a 10 c.c. syringe of cerebrospinal fluid, and then re-introducing the fluid into the sub-
dural space. This procedure, is performed with the patient in the left or right lateral
position. In most of the cases in this series, 10 c.c. of cerebrospinal fluid (only 6 c.c. in
children) were withdrawn and re-introduced twenty times. At the completion of the spinal
pumping, 10 c.c. of the spinal fluid were removed and discarded. This procedure usuall.v
takes forty or fifty minutes.

. , Of 48 cases of acute or subacute arthritis, 42 showed objective evidence of improve-
ment. The majority of the patients (70 per cent) were relieved within twelve to thirty-six
houT.s, and another 20 per cent responded at the end of seventy-two hours. The remaining
eases showed a steady improvement which was maximum at the end of two to three weeks.
^0 recoveries among chronic cases were observed but 12 of the 22 cases were considerably
relieved.

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In general, tlie results obtained confirm those recorded by Spcranlcsy. It is the opinion
of the authors, in agreement with Speransky and others, that the nervous sj'stem plays a
considerable role in the pathogenesis of rheumatic fever, rheumatoid arthritis, and other
inflammatory processes, and that spinal pumping produces some interference with the nerv-
ous mechanism which leads to favorable responses in the various forms of rheumatism
resistant to the usual forms of therapy, Bkiaet.

Kittredge, W. E., and Brown, H. G.: The Present Status of Unilateral Renal Hypertension.

J. Urol. 65: 213 (March) 1D46,

The present status of unilateral kidney pathologj' in producing hypertension is con-
sidered, with particular reference to tlie indications for nephrectomy of the diseased kidney.
This procedure has been performed in every type of surgical kidney in recent years with
the hope of relieving hypertension.

Numerous clinical investigators have pointed out that the influence of hypertension
in a scries of patients with unilateral kidney disease is actually no greater than the inci-
dence in any group of patients of comparable age chosen at random. From a study of
conflicting observations and careful follow-up of patients, the authors have reached the
following conclusions: no permanent ciiange in blood pressure can be rcasonablj' expected
to follow removal of a functionicss kidney, whether the diseased kidne}' was the original
cause of the h 3 ’pertension or not; the renal lesion associated with hypertension which was
most amenable to surgical treatment was atrophic pyelonephritis; and the next most com-
mon lesion associated with hyperten.sion was renal neoplasm, followed bj' renal lithiasis,
hydronephrosis, tuberculosis, and polj'C.vstic kidnej’s.

Although hj'pertension associated with .surgical lesions was often relieved b,v nephrec-
tomy, the blood pressure often also returns to normal following nephrolithotom.v and renal
drainage. This reduction in blood prcs.sure may persist for a r’car or more after operation
and then return to its previous level. This maj' be e.xplained on the grounds that a toxic
or irritant lesion has been eliminated and that, when this influence has worn oif, the under-
Ij’ing essential hypertension reasserts itself. Bellet.

Mokotoflf, R,, Bratns, W,, Katz, L. N,, and Howell, K. M.: The Treatment of Bacterial

Endocarditis With Penicillin, Results of 17 Consecutive Unselected Cases. Am. .1. M.

Sc. 211: 395 (April) 194G,

These authors report a series of 17 consecutive patients with subacute bacterial endo-
carditis, 14:^, of whom have fully recovered from their infection. These patients were ob-
served for a period of eight to twenty months following cessation of therap.v. The sus-
ceptibility of the organism to penicillin is one of the most important factors in determining
the outcome of therapj'. These authors agree with Loewe that the best results arc obtained
when penicillin blood serum levels are miiintnincd between five and ton times the “in
vitro” sensitivity figure. Since investigation has shown that there is little penicillin
remaining in the blood serum sixty to seventy-five minutes after a single intramuscular-
injection and practically none at the end of two hours, intermittent intramuscular injec-
tions were employed every hour on the hour du}' and night for the entire period of treat-
ment. The usual daily dose was 200,000 to 300,000 units; the more resistant cases received
1 million to 3 million units. The usual course was planned for twentj’-one daj's. It is of
some interest that one of their patients, who died because of progressively severe conges-
tive failure (six months after successful penicillin therapy) revealed at autopsy healed
subacute bacterial endocarditis of the mitral and aortic valves. Bellet.

Heuper, W. O.: Atheromatosis in Dogs PoUowing Repeated Intravenous Injections of

Hydroxycellulose. Arch. Path. 41: 130 (Fob.) 1946.

Heuper, continuing his studies on the genesis of atheromatosis, recorded the effects of
intravenous injections of hydroxj'cellulose in various concentrations. This was injected
daily for periods of six to twelve weeks. The viscositj-- of the solutions was an important

SELECTED ABSTRACTS

131

factoi' in the production of atheromatosis; the least viscid solution was responsible for the
most severe and generalized lesions. T 3 'pical foam cells, fibrous cushions, and circumscribed
hyaline thickenings of the intima, often associated with degeneration and calcification of
the media of the aorta and of the medium-sized branches were noted in the dogs receiving
injections of hydroj^'cellulose of medium, and low viscositj*. Solutions of heavy viscosity
produced no intravascular pathologic changes. On the other hand, the latter injections
resulted in leucopenia and anemia. - Goulet.

Koletsky, S.: Gross Vascularity of the Mitral Valve as a Stigma of Rheumatic Heart

Disease. Am. J. Path. 22: 351 (March) 1946.

Koletsky studied the vascularity- of the mitral valve of 150 hearts with and without
gross rheumatic heart disease, all of which showed gross vascularity of the anterior mitral
leaflet. The hearts observed were divided into three groups as follows: Group 1 contained
50 hearts with no conclusive gross rheumatic disease. Group 2 included 50 hearts with non-
deforming rheumatic mitral disease, and Group 3 included the 50 hearts with mitral stenosis.
Fifty nonrheumatic adult hearts with grossly- avascular mitral valves were included as a
control. It was found that a large percentage of hearts with no gross rheumatic disease
which presented gross vascularization of the mitral valve leaflet showed microscopically
endocardial reduplications and cellular exudate characteristic of rheumatic valvulitis. Group
2 has the same microscopic stigmata but in a higher percentage. The group of hearts with
mitral stenosis showed the highest percentage. The control group showed very; little or no
vascularity- of the anterior mitral leaflet and no microscopic stigmata.

Koletsky concludes that hearts with diffuse gross vascularity- of the mitral valve al-
most uniformly- show microscopic stigmata of inflammatory- disease of rheumatic origin.
The presence of small thick-walled arteries of musculoelastic type in the mitral valve is
considered by- Koletsky- to be characteristic and jirobably pathognomic of rheumatic fever.

Goulet:

Askey, J. M.: Quinidine in the Treatment of Auricular Fibrillation in Association With

Congestive Failure. Ann. Int. Med. 24: 371 (March) 1946.

Quinidine is ordinarily considered to be contraindicated for auricular fibrillation in
association with congestive failure, or in association with severe heart disease. In certain
instances, however, its use has. been lifesaving and in a number of desperately sick pa-
tients, it has improved the patient's cardiac status for many- months. The real dangers of
quinidine are those of embolism, sudden death, and production of ectopic ventricular
rhythms. This study concerns itself with a statistical evaluation of the dangers of quini-
dine, particularly in the presence of congestive heart failure and serious heart disease.
This is done in an attempt to determine any- deleterious effects in such patients which
would outweigh any beneficial action which may be desired. This author found that
quinidine is apparently no more dangerous to patients with congestive failure than the
natural dangers of the heart condition itself. Among patients with congestive failure who
improve adequately with digitalis and rest, along with other measures, quinidine therapy
might be tried. The presence of conduction defects appears to be a contraindication to its
use. In the absence of such abnormalities there would seem to be no reason why every
patient with uncontrolled- congestive failure should not be given a chance with quinidine.
Even if the ventricular rate is slow, reversion to sinus rhythm may- relieve congestive
failure. The usually accepted contraindications in the use of quinidine, namely- congestive
failure, repeated embolism, long standing auricdlar fibrillation, and conduction defects, are
uot considered to be absolute contraindications. Bellet.

Fox, M. J., and Bortin, M. M.: Rubella in Pregnancy Causing Malformations in Newborn.

J. A.M.A. 130: 568 (March 2) 1946.

Much interest has recently developed concerning the influence of rubella early in
pregnancy upon the production of congenital malformations. Some authors have even sug-
gested therapeutic abortion be performed when rubella occurs early in pregnancy-. In a

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AMERICAN HEART JOURNAL

series of eleven cases observed by these authors, only one evidenced a pathologic course.
Their records do not justify the conclusions of previous authors concerning the influence of
rubella in producing congenital malformation. They suggest that this subject deserves
further careful consideration and investigation. BEnnET.

Epidemiology Unit No. 82, U. S. Naval Hospital, Treasure Island: Observations on the
Treatment of Scarlet Pever With Penicillin. Am. J. M. Sc. 211: 417 (April) 1946.

In view of recent reports showing the efficacy of penicillin therapy in the treatment
of streptococcal pharyngitis and scarlet fever, an investigation was made on 118 patients
■who were members of the Naval personnel. All patients treated with penicillin showed a
good clinical response in that the temperature dropped to normal and there was marked
symptomatic improvement in twenty-four to forty-eight hours. The incidence of compli-
cations w'as found to be highest (31 per cent) in that group receiving 240,000 units in six
daj's and lowest (6 per cent) in the group receiving 480,000 units in eight days.

The rate of recurrence of positive cultures was also lowest (8 per cent) in the group
receiving the higher penicillin dosage. It was therefore concluded that the use of peni-
cillin over an eight-day period is a satisfactory method for the treatment of scarlet fever
and for preventing the establishment of a beta hemolytic streptococcus carrier state in the
convalescent patients. Beueet.

Hubaxjker, V. O. : Beitrag zur Beurteilung des nmden tiberganges von R und die ST Strecke
in Electrokardiogramm. Helvet. med. acta, Series A (March) 1946.

1. The hypothesis according to which the rounded transition of the E wave to the S-T
interval is of cardiac origin must be definitely abandoned.

2. The rounded transitions occur when polarization is small ■within the electric circuit
patient-electrocardiograph; they disappear and become pointed S waves when polarization
within this circuit is considerable.

3. The polarization capacity of the skin is small in the presence of poor blood flow
and large when the flow is good.

4. The signs of polarization in the electrocardiogram depend upon the form of the

latter (the part above and below the isoelectric line), upon the apparatus (resistance), and
upon the functional processes in the .skin of the patient (blood flow). Author.

Davidson, C. S,, Lewis, J, H., Tagnon, H. J., Adams, M. A., and Taylor, E. H. L.: Medical
Shock: Abnormal Biochemical Changes in Patients With Severe, Acu'te Medical Ill-
nesses, With and Without Peripheral Vascular Pailure. New England J. Med. 234:
279 (Feb. 28) 1946.

This study was undertaken to determine the relationship of peripheral vascular fail-
ure, uncomplicated by traumatic conditions, to the biochemical changes which accompany
shock in experimental animals and injury in man. Observations were made on a series of
twelve patients who were suffering from severe medical illness with or without the pres-
ence of peripheral vascular failure. The presence of diabetes mellitus was excluded.

It was found that the biochemical abnormalities which occurred in these patients were
similar to those wliich occur in various traumatic conditions, hemorrhage, and anoxia. They
consisted of hj'perglycemia, lactacidemia, a fall in the bicarbonate reserve, reduction in
oxygen saturation of the peripheral blood, frequent elevation of the alpha amino nitrogen
of the blood plasma, and usually a lengthening of the prothrombin time and an elevation
of the icterus index. Although the primordial cause is not known, the authors suggest the
possibility that tissue anoxia which accompanies peripheral vascular failure, leads to in-
crease in glycogenolysis and possible gluconeogenesis "with resultant hyperglycemia. A
marked correlation was found between the profoundness of the biochemical abnormality and
the degree of the rmseular failure. Laplace.

Announcements

Inter-American Congress of Cardiology, Mexico City, Oct. 6-12, 1946

There will be an Inter-American Congress of Cardiology in Mexico City,
Oct. 6-12, 1946. The meetings will be held in -the Institute of CardiologjL This
Congress is being sponsored bj'^ the Inter-American Society of Cardiology and
the National Societies of Cardiolbgjf of the Continent. Prominent European
cardiologists have been invited to attend. The American Heart Association has
been designated as the representative of this Congress in the United States, and
all applications to iDarticipate in the scientific meetings or to attend as guests
should be addressed to this Association, 1790 Broadway, New York 19, New
York.

Fellowships Available for the Study of Kheumatic FiarBR

The American Council on Eheumatie Fever of the American Heart Asso-
ciation announces that it will entertain applications for American Legion fellow-
ships for Bie study of rheumatic fever. Applications will be accepted from
recognized institutions concerned with the stud.y of rheumatic fever and rheu-
matic heart disease. Two fellowships are available. Each is for a period of
three years and carries a stipend of $3,500, $4,000, and $5,000 for the first,
second, and third .years, respectively.

Each application sliould supply information concerning the institution, the
projected stud.y, and the individual proposed for the fellowship. Applications
will be received until Aug. 1, 1946, and will become effective Sept. 1, 1946.

The American Legion fellowships for the study of rheumatic fever have
been made available by a grant from the American Legion and the Women’s
Auxiliary of the American Legion as part of their program of fostering research
in rheumatic fever and rheumatic heart disease through the American Council
on Rheumatic Fever of the American Heart Association.

Errata

Mainly hecauso of distance and tlie difficulty of rapid mail communication, there were
several errors in the paper by Dr. K, H. Goetz of Cape Town, South Africa, on “The Rate
and Control of the Blood Flow Through the Skin of the Lower Extremities,” which ap-
peared in the February, 1946, issue of the Journal, Volume 31. _ We regret exceedingly that
these errors rvere made. We are glad to publish the following corrections so that the
author’s intended meaning will be clear.

1. Page 154, the second line of the last paragraph should read “multiple pinpricks”
and not “multiple principles.”

2. Page 164, hve lines from the top of the page, should read: “Fig. 14 shows one of
the arteries of the digit tested” and not “Fig. 14 shows the results of testing one of the
arteries of the digit.”

3. Page 172, the sixth line of the second paragraph should read: “This decrease in
blood flow following body heating has been explained as follows: Since body heating causes
a release of the vasomotor tone in the normally innervated extremities, it follows ... to the
unsympathectomized one. ’ ’

_ 4, Page 177, the last sentence in the flrst paragraph under Discussion should read:
^ ^Failure of the pulse has therefore to be accounted for” not “Failure . . . has yet to be . . .”

0 . Page 177, the flrst line of the last paragraph should read : ‘ ‘ The possibility of such

a wide range in blood flow, under the control of the autonomic nervous system, is part of the
body’s mechanism for temperature regulation.^’ Not “The possibility exists ...”

133

American Heart Association, Inc.

1790 Broadwav at 58th Strect, New York, N. Y.

Dr. Rot 'W, Scott
President

Dn. Howard D. AVkbt
Tioc-Presuient

Dn. George R. Herrmann
Treasurer

Dr. Howard B. Sprague
Scoretary

BOARD OF DIRECTORS

*Dr. Edgar V. Aleen Rochc.slcr, Minn.
DR. Arlie R. Barnes Roclicstec, Minn.
Dr. IViLEXAsr II. Bu.n'n

Voiing.stown, Oliio
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Mew York City
Dr. Norman E. Freeman Plilladclphia
•Dr. Tinslep R. Harrison D.allas

Dr. George R. Herrmann Galvc.ston
Dr. T. Duckett Jones Boston

Dr. Louis N. Katz Cldcaso

•Dr. Samuel A. Levine Boston

Dr. gilbert IMArquardt Chicago

•Dr. H. :M. AIarvin New Haven

•Dn. Edwin P. :Maynard, Jr. Brooklyn
•Dr. Thomas M. McMillan Philadelnhla
Dr. Jonathan Meakins Montreal

Dn. E. Sterling Nichol Miami

•Executive Committee

Dr. Harold E, B. Pardee

New Y^ork City
Dr. tViLLiAM B. Porter Richmond, Va.
Dr. David D. Rutstein New Y'ork City
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•Dn. Roy AV. Scott Cleveland

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Dr. George F. Strong

Vancouver, B.C.. Can.
Dn. AA'illiam D. Stroud Philadelphia
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Dr. Harry e. Ungerijeider

New Y'ork City
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Dn. PAUL D. AA'hite Boston

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•Dn. Invi.No S. AAauGHT New Y'ork City
Dn. AA^^LLACE M. YATER

AVashington, D. C.

Dr. H. M. Marvin, Acting Executive Secretary

Anna S. AA'^right, OSico Secretary ^

Telephone, Circle 5-SOOO

T he American Heart Assoeialion is the only national organization devoted to
educational work relating to diseases of the heart. Its activities are under
the control and guidance of a Board of Directors composed of thirty-three eminent
physicians who represent every portion of the country.

A central office is maintained for the coordination and distribution of important
information. From it there issues a steady stream of books, pamphlets, charts,
films, lantern slides, and similar educational material concerned with the recognition,
prevention, or treatment of diseases of the heart, which arc now tlie leading cause of
death in the United States. The American IIe.art Journal is under the editorial
supervision of the Association.

Tlie Section for the Study of the Peripheral Circulation ivas organized in 1935
for the purpose of stimulating interest in investigation of all types of diseases of
the blood and Ijunph vessels and of problems concerning thq circulation of blood
and lymph. Any physician or investigator may become a member of the section
after election to the American Heart Association and pajment of dues to that
organization.

The income from membersliip and donations provides the sole financial support
of the Association. Lack of adequate fimds seriously hampers more intensive
educational activity and the support of important investigative work.

Annual membership is $5.00. Journal membership at $11.00 includes a year’s
subscription to the AarERic.:VN IIjiart Journal (January-December) and annual
membership in the Association. The Journal alone is $10.00 per year.

The Association earnestly solicits your support and suggestions for its work.
Membership application blanks will be sent on request. Donations will be gratefully
received and promptly acknowledged.

134

American Heart Journal

VoL. 32

August, 1946

No. 2

Original Communications

THE PEBCORDIAL ELECTEOCARDIOGKAM IN HIGH LATERAL

MYOCARDIAL INFARCTION

Francis F. Rosenbaum, M.D., Frank N, Wilson, M,D., and
Franklin D. Johnston, M.D.

Ann Arbor, i\ricH.

T he obsen’ations upon wliieh this report is based wore made on a group oi
six patients 'wliose routine standard and unipolar extremity electrocardio-
grams showed changes suggestive of myocardial infarction. Tlie usual pre-
cordial leads presented no more and often much lc.ss evidence pointing to thi.s
diagnosis. On the other hand, extensive exploration of the left anterolateral,
lateral, and posterolateral aspects of the thorax at levels higher than those
usually studied yielded more significant electrocardiographic data.

Four of the six patients gave a definite liistory of a coronary accident a feu-
days to one year prior to the time of our observations; one of them ha.s recently
developed a posterior lesion one year after an earlier high posterolateral lesion.
In two eases the history was merely suggestive of infarction; one patient had
angina pectoris, intennittont claudication, and an old posterior infarct, and the
other had moderate eongesti^'e failure alone.

In four xiatieiits the changes most eharactoristic of myocardial iniarction
were recorded in the vertical line of Lead Vs, Lead or Lead V-. but one to
three intercostal spaces above the level from which these leads are taken. In
these ease.s a diagnosis of liigh anterolateral infarction wa.s made. In one patient,
the most striking changes oeeurred in leads from the anterior and midaxillary
lines at levels two or three intercaslal spaces higher than the usual Lead \ r, or
Yc; in this iiistanee, the diagnosis was high lateral infarction. In one case the
most definite changes were seen in records from points liigh in the left posterior
axillary and the left scapular lines and were attributed to a high po.steroloteral

■ From the Department of Internal aiediclne. Univerpitr of Slichipan JfedK-.n! ScJ.mjL Much
of the work upon whicli this article. is based was done under . a grant from tSic H.

micldiam School of Graduate Studies,

: , Presented in part before the Eighteenth Annual Meeting of the Central Society for ('lini-
cjil Itescarch, Chicago, Nov. S, 1945.

Received for, publication Feb. S, 1946.

135

13G

AMERICAN HEART JOURNAL '

infarct. The observations made were' not identical in all patients since only
as the study progressed were the most advantageous points for exploration re-
vealed.’*'

i

. ChmiOA-L OBSERVATIONS

1 High Anterolateral Infarction . — The first four cases to be discussed are con-
sidered examples of high anterolateral infarction.

Case 1. — H. K., a 41-year-old bus driver entered the University Hospital on June 23j 1944,
for treatment of a left hemiplegia which Imd appeared suddenly one year earlier. For two
weeks prior to the occurrence of the paralysis lie had experienced frequent attacks of pain in
the chest while driving his bus. The attacks were severe enough to make him stop to rest
smd he was finally forced to stop Avorking because of them. In May, 1943, while sitting in a
restaurant, he suddenly developed a left hemiplegia. He Avas under tre.atment in a hospital
for one month; his blood pressure avus said to liaA'c been high during that period. He was
able to Avalk AAith difficulty by August, 1943, but there had been little change in his condition
for ten months. There was a strong familial history of cardiovascular disorders.

Examination slioAved a left spastic hemiplegia AA-ith a left facial paresis of central type.
The retinal A’essels exhibited minimal arteriosclerosis. The heart sounds were normal. The
blood pressure Avas 120/80. There Averc occasional extra.systoles. The usual laborator}* te.sts,
including the blood Kahn reaction, were negatii’C. Roentgenogiaphic examination of the
thorax shoAved slight cardiac enlargement and slight pulmonary congestion. - '

, Eleetrocardiograpliie studies were made on July 28, 29, and 30. Only those
made on the last day, when supplementary prceordial leads were taken, are
reproduced (Pig. 1). The standard and unipolar limb leads exliibit slight left
axis deviation with small Q waves and slight terminal inversion of the T waves
in Leads I and Vl. The usual precordial leads show tiny Q waves in Leads Va,
Vg, and V 4 and terminal inversion of the T waves in Leads V 3 , V 4 , and V 5 . In
the ease, of normal subjects there is a rapid increase in the size of the R Avaves
as the exploi'ing electrode is moved tOAvard the left side of the precoi'dium. In
this ease, therefore, the R Avaves are unexpectedly small in Leads V3, V 4 > and V.-,.
It should also he noted that R is taller in Lead Vo than it is in Lead V.-,; the
opposite is normal.^

The tracings from points in the left midclaAdcular line (vertical line of
Lead V 4 ) at higher levels (third and fourth intercostal spaces) shoAV both QRS
and T-AvaA'e changes Avhich are strongly suggestive, if not diagnostic, of myo-
cardial infarction. Similar hut less striking alterations occur in the leads from
points at the same horizontal levels hut in the left anterior axillary line (line oi
Lead Vg). Only very slight inversion of the T AA^A^es is seen in tlie record from
a point in the midaxillary line (line of Lead V 5 ) and at the leAml of the third
intercostal space.

Case 2. — C. K., a 40-year-oia engineer entered the Heart Station of the University Hos-
pital on March 3, 1944. Tavo months preA*iously he developed burning substernal pain which

.•After the first few cases had been studied, w-e adopted the plan of taking- supplemen-
tary unipolar leads from points at the Intersections of lines on the horizontal level of the
fourth, third, or second intercostal space at the left sternal margin and the vertical lines of
X.ead Vs. Lead V4 (left midclavicular line), .Lead Ve (left anterior axillarj* line), Lead Ve (left
inldaxillary line), Lead Vi (left posterior axillary line), etc., as indicated.

138

AMERICAN HEART JOURNAL

radiated to the left aim and lasted twenty houib. He had been in a hospital for thiee weehs
and v\a3 giadually resuming activity. There was no hibtoiy of caidiac symptoms before the
coronary accident.

There was no cardiac enlargement. The caidiac sounds were lather loud and the heart
seemed overaetive. There was a faint systolic murmur at the base. Tiie blood pressure was
170/100.

The electrocardiograms made during the patient’s acute illness were avail-
able and are reproduced along with the observations made at the time of our
examination in Fig. 2 . Tlie tracing taken on the day of the attack (Jan. 5, 1944)
displays very slight upward RS-T displacement in Lead I and slight downward
RS-T displacement in Lead III, but is not certainly abnormal. On Jan. 11, 1944,
the changes in the RS-T segment had become somewliat more distinct and a
tiny Q wave had appeared in Lead I. Tlie standard electrocardiogram taken
eleven days later shows, in addition, definite terminal inversion of the T waves
in Lead I, and upright T waves in Lead III. A single precordial electrocardio-
gram (IV) was made from a point said to be in tlie vertical line of V 3 but two
intercostal spaces higher than the usual level; it displays QRS and T-wave
changes characteristic of recent myocardial infarction. The records taken at
the time of our examination on March 3, 1944, display only small Q waves in
Leads I and Vr,; the usual precordial leads, Vi to Vc, are well within normal
limits. The records made from a point high in the anterior axillary line and
from a point in the line of Lead V 3 but at the level of the second intercostal
space at the left sternal margin show prominent Q waves and normal T waves.
These changes are regarded as residual electrocardiographic evidence of the in-
farction which had occurred two months earlier ; apparently, the alterations of
the T wave in this ease were quite transient. It is notable that only the chest
leads taken at higher levels and Lead Yr, display signs -which can be considered
significant. The record from a point higli in tlie midaxillary line does not show
changes of similar degree.

Case 3. — T. S., a 37-year-old chiropodist entered the University Hospital on Jan. 18,
1945 , complaining of attacks of dyspnea and hemoptysis. Albuminuria and fluctuating hj-per-
tension had been discovered five years earlier, and one year prior to admission he began to
have paroxysmal nocturnal dyspnea. He had a typical myocai'dial infarction in July, 194.4,
after which the attacks of paroxysmal left ventricular failure grew more severe and were
precipitated by excitement and emotional stress.

The patient was a small, hyperkinetic man. Marked hypertensive retinopathy was
present. The heart was tremendously enlarged. A moderately loud systolic murmur and a
diastolic gallop sound were heard at the apex and along the sternum. There were frequent
extrasystoles. The blood pressure was 190/130 in the right arm and 130/100 in the left arm.
A difference of tiiis order was consistently present and was not altered by the position of the
arms. During periods of stress the blood pressure rose as high as 290/210. Conspicuous
peripheral arterial thickening was present.

Slight albuminuria and moderate reduction of urea clearance were found. A histamine
test failed to give a response suggestive of a pheochromocytoma .2 Other laboratory studies
of the blood chemistry and pyelograms were negative. Roentgenographic examinations of
the thorax disclosed great cardiac enlargement and moderate pulmonary congestion.

A bilateral splanchnicectomy was performed on Peb. 12, 1945. The operation and con-
valescence were uneventful. The patient was re-examined in the Heart Station on April 12,
1945. He was then generally improved, and the attacks of left ventricular failure were fewer

ROSENBAUM ET 'AL. : PRECORDIAL ECO IN MYOCARDIAL INFARCTION 139

and less severe. The physical findings were not significantly different from those elicited
prior to the operation. The blood pressure was 185/135. His referring physician recently
informed us . that he died, on Aug. 8, 1945, from a cerebral hemorrhage.

Electrocardiograms made at the time of the acute infarction were available
for review. On July 27, 1944, the standard leads displayed prominent Q waves.

shght elevation .of the RS-T segment, and terminal inversion of the T waves in
Leads I and II with marked depression of the RS-T segment in Lead III. The
precprdial leads showed unusual large QRS deflections with R waves which were
definitely smaller in Lead V 3 than in Lead V 2 or V 4 , tiny Q waves in Leads V 4 ,
■Vs, arid Vc, and normal T deflections except for diphasic T waves in Lead Ve-

140 AMERICAK HEART JOURNAL

- f

Except for the relatively small R waves in Lead Vs, the imecordial leads did not
• suggest fresh myocardial infarction, although the standard leads were compatible
' \vitli that diagnosis. . The electrocardiograms, taken on Sept. 11, 1944, displayed
tlic usual progression of changes in the standard ,lead.s, - The precordial leads on

this occasion again showed a tiny R wave in Lead Vs hut, m addition, large Q .
dbfleetions in Lead V 4 and deep, sharp, terminal inversion of the T waves in
Leads Vr, and Vc. , The differences between the .two 'sets' of .precordial leads maj .

:V • . ROSENBAUM ET AL. : PRECORDIAL PX’G IN , MYOCARDIAL INFARCTION 141 •

.. have been due to differences in. the locations of the preeordial points selected/
on the two occasions or, what seems less likely, to changes in the sff:e or ehar-
. acter/of the myocardial lesion. . . ...

. ^ , Our own eleetrocardiogTams were taken on Jan. 20, 22, and 23, 1945. All .
of the records are nuich alike and onb' the la.st .sot of tracings is reproduced ’
.(Fig. 3). LcadhI and Vi, show small Q waves and very slight terminal in%xrsion
of the T waves. There is slight depression . of tlie RS-T segment in Leads II, III,
and Vp, but this may be the result of digitalis' therapy. The usual precordial,
leads disiilay smaller ,R waves m Lead Ys than in Lead V2 or V4, tiny Q wave.s
in Leads V.i, V5, and Vo and slightly inverted T waves in Leads V5 and Vc.
Curves of this type may occur in left ventricular hj^'pertrophy, but when they
; do the R wave usually grows progressively larger as the exploring electrode is
movxd to the left. Diminution of its size such as is seen here in Lead V3 is rare
, in the absence of anterior infarction.^ The implications of this finding become
apparent when, one. examines the records taken at higher levels in the line of ,
Leads Y 4 and Vo, for in these tracings there are large QS deflections very sug-
gestive of infarction. As in Case 2, the inversion of the T waves previously ,
present had cleared before the extensive electrocardiographic observations were
made.' ■

■ Case 4. — 'W. T., a So-year-old engineer was, first seen in the Heart Station of the Uni-
versity Hospital on July 20, 1943. He complained of pain in the chest and calve.s. Five
years before this, he had a quite typical myocardial infarction, and one year later he had
■ similar but le.ss severe symptoms. After the second attack he developed mild angina pectoris
• and intermittent claudication, • ,

: '. The patient was a short,, stocky florid man. Tlie heart was not enlarged. The cardiac
sounds ■were rather distant. The blood pressure was 124/80. A few rales were heard at both
•...lung bases posteriorly. No pulsations could be felt in the left posterior tibial or in either
.‘of the dorsalis pedis arteries.

-The, standard and unipolar limb leads (Fig. 4) display small Q waves in Leads II and Vp
', and prominent Q waves and inverted T wfives in Lead III. The precordial leads show only

■ 'flat or. slightly 'inverted T -waves in Leads and Vg. In view of the previous clinical history,

■ . tliese changes may represent an old posterior mj'ocardial infarct, but they are not of them-
, selves ' diagnostic of this condition.

The patient; returned to the Heart Station on Aug. 24, 1945. He had continued to have
: , .mild angina pectoris and intermittent claudiention. Four months earlier, while walking in his
. .'faetoi-y,' he had a sudden attack of severe dizziness and had to be assisted to his office. He
noted diplopia for .'about one hour and a giddy sensation for several days. This latter coni-
, - ; plaint had- persisted in mild degree up to the time of admission.

' The bindings on examination were much the same as on his initial visit. The blood pre.*^-
.sure was 11 0/8,0. . There: was no evidence of postural hypotension. The hemoglobin, blood
Kahn reaction, and miniature chest roentgenogram were normal.

T^^ extremity electrocardiograms (Pig. 4) are dis-

/ ;tinctly different from those taken two years earlier. There are small Q waves >

/ / ^d flat T tyave.s in Lead I, and the Q waves previously present in Leads II, III,

;■ and .Yp bave,: d^ Lead Yt exhibits prominent Q waves and sharp

waves. The usual preeordial leads differ from those
^ / in; that, the R waves failed to increase rapidly in size as the

" y fexploinng ^ee^ moved to tlie left and the T waves are smaller. The .

14:2 AMEEICAN HEART JOURNAL

ES-T segment in Lead V4 has a peculiar flattened outline and is somewhat de-
pressed, Since these precordial records did not exhibit diagnostic evidence of
infarction, leads from points at liigher levels were employed. The records from

points in the line of Lead V,, but at the levels of the fourth, third, and second ,
intercostal spaces at the sternum, and in the line of V5 at similar levels, s ow
changes in the QRS and T complexes which are in all respects characteristic oi

■ ROSENBAUM ,ET 'AL. : PRECORDLUj EGG IN MYOCARDIAL INFARCTION 143

mydcardial infarction. Curves made from the midaxillary line at these higher
■levels do. not display changes of like magnitude.

The date of the infarction responsible for tlie electrocardiographic changes
recorded in 1945 is not clear. It may have occurred at the time of the severe

144

AJIERICAN HEART .JOURNAL

attack of dizziness, ov the patient may have regarded the symptoms associated
with it as merelj' one of Ids many attacks of angina pectoris.

High Lateral Infarction . — One ease is considered an example of high lateral
infarction because the most striking electrocardiographic changes occurred in
unipolar leads from the upper lateral aspects of the left thorax and left axilla.

Case 5. — J. L.. a (i7-yc:ir-ol(l tailor cnleicd the Univer.sity Hospital on March 4, 1945,
complaining of dy'spnca and \i8unl diflSculty. He had noted exertional dyspnea and inter-
mittent ankle edema for many years. For one year there had been paroxysmal nocturnal
dyspnea. Ten months before ho nas fust seen, he had been in a hospital for ten days because
of these complaints. There nas- no history suggesting an acute myocardial infarction.
Cataiacts had caused progressive reduction in vision.

' The patient nas moderately dyspneic and appeared chronically ill. Minimal pulmonary
congestion and emphysema nere noted. The heart sounds were normal; no murmurs were
heard. The blood pressure nas 140/84, There nns peripheral arteriosclerosis and minimal
pitting edema Of the ankles. The urine, blood, stool, and blood Kahn examinations were nega-
tive. Eoentgonographic examination of the thorax showed marked cardiac enlargement and
slight pulmonary congestion.

The patient responded ucll to treatment for congesti\c cardiac failure. He was dis-
charged on March 17, 1945. He returned for a cataract extraction on May 14. 1945. H'hen
last seen on Aug. 20, 1915, his condition was unchanged.

The standard limb and precordial leads taken on Marcli 6 and March 13,
1945, are similar to those taken on ^lareh 14, 1945. which arc reproduced in
Fig, 5. In Lead I tliere are a tiny R wave preceding a deep S deflection, slight
upward RS-T displacemeut, and slight terminal inversion of the T waves. Lead
Vi, is similar except for the absence of tlie small initial R. Leads II, III, and Vf
show slight RS-T depression, possibly due to digitalis which the iiatient was
receiving. The standard precordial curves are distinctly abnormal since the
R wave grows progressively smaller in successive leads, becoming smallest in
Lead V,^. There is pronounced upward displacement of the RS-T segment in
Leads V3, V4, and Vn and terminal inversion of the T waves in Leads Vo and Ve
in addition. Inasmuch as these changes were strongly suggestive of myocardial
infarction, hut did not include the presence of prominent Q or QS deflections
in the leads from llie usual procordial sites, additional tracings from points at
liigher levels were taken. The characteristic changes sought were recorded from
regions high up in the line of Lead Vr, (see Vr, — 2I.C.S.) and in -the vertical
line of Lead Ve (see Vo — 3 I.C.S.).

High Posterolateral Infarction . — One case has been classified as an example
of high posterolateral infarction hccanse the most characteristic electrocardio-
graphic phenomena appeared in records taken from points high in the loft pos-
terior axillary line and over the left 'scapula. This ease was unusually interest-
ing because of the length of the interval which elapsed between the onset of
symptoms and the appearance of the electrocardiographic changes. The patient
recently developed a typical posterior myocai*dial infarct.

Case 6. — J. a., a 46-year-old moulder, uas admitted to the TJniversity' Hospital on Sept.
16, 1944, complaining of severe retrosternal pain. Three years previously he began to have
incapacitating intesmittent claudication. On Sept. ,10, 3944, he had attacks of severe, crush-

: • prkcordial;ecg IN. myocardial infarction ' ■ .145

' Ting, retrosternal painAvliicli radiated to tlic.left arm and liand. Tliese attaclis were severe
' . and -prolonged and were only partially relieved by opiates. Five days before admission, the
blood -pressure was said to bo 210/110.

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. ;:. The patient was a heaxy, iriu.seular man and was in acute painful di-stress. The heart
.was not enlarged and the cardiac sounds were normal. The blood pressure was luO/OO. The
? left leg/was sorhewiiatJ cool, , and the pulse in the left dorsalis pedis artery was absent. The
; routine: urine, stool, blood Kahn, chest roentgenographic, and blood examinations were negative

/ for slight leucocyto.sis during the first week in the ho.spital.

146

ROSENBAUM ET AJL. : PEECORDIAL EGG IN MYOCARDIAL INFARCTION 147

The usual treatment for myocardial infarction was instituted. Two lesser attacks of pain
occurred durring the patient stay in the hospital. There was some fever, maximum rectal,
temperature 103.2° F., during the first five days. The patient was discharged on the twenty-
third hospital day. '

■ A few of the records which display the progression of changes in this case
are shown in Fig. 6. The standard and unipolar limb leads taken on S^pt. 16,
1944, are not abnormal. The same leads taken on September 18 exhibit deflec-
tions of similar outline except for slight changes in the RS-T segment in Lead 1
and some flattening of the T tvave in Lead II. The precordial leads of September
19 (Fig. 7) show a, small depression of the RS-T segment m Leads Yj and Y._.
and Yiery slight elevation of this segment in Lead Yc, but these curves are not
certainly abnormal. The standard and unipolar" extremity leads of September 25
and September 27 are -much alike and both display terminal inversion of the
T waves in Leads I and Yl. The T waves in Leads II, III, and Yp have become
very large, tall, and upright. Furthermore, .the usual precordial tracings of
September 27 are vez’y different from those taken eight days earlier, for the
T \vaves are much taller in the leads from the right side of the precordium and
there is slight terminal inversion of the T -wave in Lead Yc- These changes
represent the first unequivocal electrocardiographic evidence of the myocardial
infarction which, judging from the clinical data, occurred at least ten days be-
fore they appeared. Additional records from points in the axilla, high in the
mid-axillary line (Lt. mid. axill. line), in the posterior axillary line (Lt. post,
axill, line Level — 4 Cost. st. angle), and over the left scapula (Mid. point Lt.
seap.) exhibit more characteristic changes in the T complex but 210 significant
alterations of the QRS deflections (Fig. 7).

, The patient was readmitted to the University Hospital on Sept. 4, 1945, complaining of
severe pain in tlie chest. He had been comfortable except for mild angina pectoris until
three days before when he had anginal pain lasting ten minutes. On tlie day of admission he
had a very severe attack which persisted several hours despite repeated lij’poderraic injections.

The patient was slightly dy.spneic. Fine rales were heard at the bases of both lungs.
The heart was slightly enlarged and some precordial tcnderaess was noted. The blood pres-
sure was 132/70. The blood, urine, stool examinations, and the circulation time were normal.

. ■' : The, patient was again treated for myocardial infarction in the^ usual manner. There

was' some recurrence of pain during the third week, but the hospital course was not other-
, wise remarkable. He was di.scliarged on the twenty-sixtli day.

' The standard and' unipolar limb leads of Sept. 5, 1945, are characteristic
of recent posterior myocardial infarction and show prominent Q waves and deep
, terrriinal inversion of the T waves in Leads II, III, and Yf (Fig. 6). Records
taken on September 6 and September 21 are similar except for greater inversion
of the T deflections. The precordial leads (Fig. 7) are similar to those taken
on Sept. 27,, 1944, except that terminal inversion of the T tvaves is present in
: Lead.s Y5, Yc, and Ye. Leads from points low in the left posterior axillaiy line
also show typical T-wmve changes but those from points at higher levels, wdiich
; exhibited significant changes after the first infarction, fail to show* such altera-
tions. The contrast of changes in Leads Yl and Yf produced by the two infarcts
' and the -appearance with the second infarction of deep inversion of the T waves
iivthe lead from the ensiform cartilage (Ye) are additional features of interest.

148

AitRlilCAK HEART JOURKAL

, MRCUSSIOX

Wood, Wolfei'lli, and Bellet’ have proposed criteria for tlie electrocardio-
graphic diagnosis of acute lateral or midventricular infarction. The features
which they considered important wej-e dein-es.sion of the RS-T segment in
Lead IV, and usually in Leads I and TI, and the absence of signs of posterior
infarction in Lead III. Using these criteria Thomson and FeiB reviewed the
electrocardiograms of nineteen patients who were found at post-mortem examina-
tion to have lateral myocardial infarction. Their studies did not disclose a con-
sistent correlation beUveen the po.st -mortem and' the electrocardiograph ie find-
ings; only four of nine patients with recent lateral infarction showed the pat-
tern described by Wood, Wolferth, and Bellet. Boseo’' has employed the .same
criteria in an effort to estaljlish lateral infarction as a distinct anatomieoclinieal
jentity different from infarction involving the anterior or posterior walls of tlie
left ventricle. It has been recognized'’’ that cliangcs of this same type may
result from digitalis, may occur in records made during attaelcs of angina
pectoris, and may appear under other circumstances. Wilson” has pointed out
that the most reliable signs of myocardial infarction consist of a sequence of
characteristic alterations in both tl\e QRS and T complexes. It has been onr
experience in this laboratory that lateral infarction of the more usual variety
produces these characteristic changes in unipolar precordial leads from the
left lateral thorax (Leads Vr„ Vo, and V 7 , which is from the posterior axillaiy
line) at the level of the cardiac apex,^ The records of the group of cases pre-
s sented in this report are quite different from tliose of the more usual examples
of lateral infarction, and we believe that they represent an important, although
probably somewhat uncommon type of lateral myocardial infarction.

If the electroeardiograidiic observations made in these six patients are re-
viewed, certain features appear to be significant. The standard electroeardio-
gi-ams of all but one of tlie patients show tiny or small Q waves and flat or
slightly inverted T waves in Lead I. The magnitude of the changes in the T
complex varies from ease to case, liut this would be expected -since the electro-
cardiographic studies were made at very different stages of the infarction in the
different instances. Although there are no Q waves in Lead I in the records of
Case 5 which are reproduced, they were present in tracings taken earlier. Tliis
difference may he accounted for by a shift in the position of the heart. The
ventricular complexes of the unipolar lead from the left arm (Vi,) are similar in
general outline to those of Lead I in all cases and exhibit small Q waves and
flattening, sight inversion, or sharp terminal invei-sion of the T deflections.
On the whole, the changes in Lead Vi, are more striking than those in Lead I,
and, in the instance of high lateral infarction (Case 5), the difference is pro-
nounced, probably because the zone of infarction was in such a position as to
face toward the left shoulder as well as toward the upper left axilla.

The character of the complexes of the standard precordial leads dis-
tinguishes these cases from the usual tj-pe of lateral infarction. There are no
changes diagnostic of infarction in the QRS complexes of the leads from the
left side of the preeordium, and, in all but two eases (1 and 5), distinctive altera-

ROSENBAUM' ET AL. : PRECORDIAL EGG IN MYOCARDIAL INFARCTION ' .149

tions ill the T complex are- absent in the leads from this region. Oii the wiiole,
-the deviations from the normal in the standard prceordial leads were least im-
])ressive in the cases of liigh anterolateral infarction. In one instance (Case 2)
these leads are normal, iii two' (Oases 3 and 4) they shmr only tiny Q waves and
minor changes in the T Avaves of the leads from the left side of the precordiiim,
and in the remaining one (Case 1) the R waves are unusually small in all of
these leads. Terminal inversion of the T waves is also seen in Leads V4 and
in this case. The usuaL precordial leads in the case of high lateral iiifafction
(Case 5) display, a pi'onounced decrease of the height of the R wave in successive
leads. This case exhibits slight to moderate inversion of the T waves and some
upward 'displacement of the RS-T segment in the leads from the left side of
the' preeordium. This displacement is apparently of the persistent type since
the clinical data do not suggest that the infarction was recent. There were,
liowever, no roentgenographie signs of ventricular aneurysm, such as have been
oliservcd in some instances of persistent displacement of the RS-T segment." In
the, single instance (Case 6) of high posterolateral infarction, the usual pre-
cordial leads showed at first only slight depression of the RS-T segment in Leads
Vi and Vo. Subsequentl.y when the changes in other leads had become apparent,
the T Avaves of the leads from the right side of the pTecordium became taller
and slight terminal inversion of the T deflection appeared in Lead Vc.

>So far as the supplementary leads taken from the upper left thorax are con-
cerned, it maj^ be said that, in all but one instance (Case 3), Q or QS and^T-ivaA^e
.changes eharaeteristie of myocardial infarction were recorded. In the single
exception, only QRS changes Avere present, presumably because the infarction
’ had occurred six months before. Earlier records of the usual type displayed
, characteristic alterations in the T AAmA-^e. It Avas necessary to place the exploring
electrode one to three interco.stal spaces aboA'^e the usual levels to obtain diag-
nostic electrocardiographic changes. In some instances (Case 6) the zone AAfiiich
yielded the most significant changes Avas relatively small AA’-hereas in others
(Cases 1 and 4) it AA’as much larger. This difference may have depended upon
the relative size of the infarcted region, but we have no evidence bearing on this
question. The distinction betAA’-een anterolateral, lateral, and posterolateral in-
Tafcts is here based upon the position of the vertical lines through the points
AA^iich yielded the most pronounced electrocardiographic changes. If the most
pronounced CAddence of infarction occurred in leads from points lying directly
above those used in taking Leads V3, V4, and Vr„ the case was put in the first
group ; if it, occurred in leads from points above those used in taking Leads Y.-
and Yc, it AA^a.s placed in the second; and if it occurred in leads from points in
\ the left posterior, axillary line (V7) and the left scapular line, it Avas placed
m the tlnrd, group.

. Our experience Avith electrocardiograms obtained by means of iinijmlar leads
fTOin the higher levels of the chest has been rather limited. In order to control
.the pbseryations made in our eases of high lateral infarction,' Ave have examined
.tracings’'^ obtained in, a similar Avay from a small group of normal subjects and

. . .‘Some of the' tracings .utilized were taken in this laboratory®; others were taken by Miss

-wnic Ma,ry, Lyle of the Prudential Insurance Companj'.®

150

AMERICAN HEART JOURNAL

from a group of patients with various kiiids of elect i‘oeardiographie abnormali-
ties. Prominent Q or QS whvos were not encountered in leads from the higher
levels of the left anterolateral and lateral thoracic area.s when the heait was
normal. In general, the ventricular complcxc.s of leads from the higher levels
of the loft anterolateral and lateral thoracic areas are transitional in form be-
tween those of the .standard unipolar lead from the left side of the precordium
and those of the unipolar lead from the left arm (Lead ViJ. Wlicncver, for
any one of a variety of reasons, there arc large Q waves or QfS deflections in
Lead Vj,, ])rominent Q -waves Avill usually bo present in some leads from the
upper levels of the left thorax. It is, therefore, our present opinion that promi-
nent Q waves, QS deflections, and shar]>ly inverted T Avaves in Leads of tlie
kind in (piestion have an inpiortant hearinsj uimn the diagnosis of myocardial
infarction only when they give rise to ventricular complexes which are more
typical of this lesion than the ventricular complexes of either the standard pre-
cordial leads or the uniiiolar lead from the left arm. The chief indication foi-
additional leads from the upper levels of the left thorax is the jiresence of
changes suggc.stive of infarction in Lead Vt. without corresponding changes in
the standard leads from the left side of the precordium.

There are several possible explanations for the occurrence of the most
striking signs of infarction in leads from thoracic levels above those irsually
explored. We believe that this phenomenon is usually due to infarction of pails
of the Avail of the left ventricle which arc closer to the base of this chamber than
those more commonly involvqd. Some of the infarcts studied by Thom.son and
FeiP'seem to have been of this sort, and avc have recently heard of instances of
liigh lateral infarction demonstrated at aulop.sy in whicli llie standard extremity
and precordial electrocardiograms resembled some of those described in this
article.^'’ It is, of cour.se, possible that the jieeuliarilies of the electroeardio-
graphie patterns Ave have described are sometimes the re.sult of rotation of the
heart or some other change in the spatial relations of its surfaces to the slandai'd
elcelroeardiographic leads. It is also difficult to predict what modifications of
the more common electrocardiographic patterns produced bj’ infarction miglit
arise as a consequence of A'cntrieular enlargement folloAving a coronary accident.

The delayed appearance of electrocardiographic evidence of myocardial in-
farction in Case 6 (Figs. 6 and 7) is, perhaps, deserving of comment. The
clinical findings Avere sufficiently characteristic at the time of the patient’s first
admission to the hospital to justify the diagnosis made, ])ul sup])ortivc electro-
cardiographic data were not olitained, despite frequent examinations, until ten
days later. Some considerations Avhich may account for the delayed appearance
of electrocardiographic signs of infarction have been discussed clscAVhcre.” It
has'been pointed out that in leads from the precordium and extremities, in con- ,
trast to leads from the surface of the heart itself, the effects produced by the
parts of the infarct responsible for RS-T displacement may obscure those pro-
" dueed by the muscle responsible for iuA'ersion of the T deflection. Tliis is likely
to happen Avhen the muscle zone ischemic enough to give rise to changes of the
first kind in direct leads is approximately equal in size to the zone ischemic
only to the degree necessary to giAm rise to changes of the second kind. A loon- ^

-KOSENBAUM ET AL. : PRECORDIAL ECG IX MYOCARDIAL INFARCTION ■ 157

tion of tiie iiifarcted region Avliich is nnfavorabie with respect to the leads em-
ployed may also aceomit for the late appearance of characteristic eleetrocafdioT
_§raphic evWenee of infarction. Finally, the extension of an initially small in-
farct may explain the apparently late development of electrocardiographic
changes in some instances. In the ea.se imder consideration the location of the
infarct was muisn'al and certainly unfavorable as far as its detection by means
of the usual extremity and precordial leads was 'concerned. It seems probable,
however, that the factor first mentioned was an important cau.se of the late
appearance of . inversion of the T wave in Leads I, Yi., and ¥«.

.SUMMARY

Six ca.ses of suspected infarction of the ba.sal parts of tJie lateral wall of the
left ventricle are reported. The nsual unipolar limb leads and tlie six standard
precordial leads failed to furnish unequivocal evidence of myocardial infarction
in these eases. Unipolar leads from points on the anterolateral, lateral, and
posterolateral a.speets of the upper left thoi’ax supplied electrocardiographic
data of greater diagnostic value.

The types of lesions differentiated have licen classified as liigh anterolateral,
higli lateral, and high posterolateral infarcts on the basis of the vertical lines in
which the most significant electrocardiographic changes wei-e recorded.

The opinion is exprcs.scd that in the.se in.stanccs the electrocardiographic
changes tyiiical of infarction were mo.st pronounced in leads from the upper
left thorax because the Infai'ctcd region was more basal and more lateral than
is usually the case. It is, however, admitted that rotation of the heart or some
other change in the relations of its surfaces to the usual leads may have been
responsible for some of the electrocardiographic peculiarities encountered.

It is recommended that unipolar leads from the higher levels of the left
thorax be taken when the clinical hi.storv and Lead I, or Lead Yl, both suggest
: that, myocardial infarction has occurred and the .standard leads from the left
side of. the ])recoi’diura fail to display changes of the kind and magnitude ex-
pected. '

. - , REFERENCES

]. "Wilson, N., .Tolinston, F. I)., Ko.senbaum, F. F., Erlnnger, H., Kossnian, C. E., Heclit, H.,
... Cotrini^ N., Meneze.s do Oliveira, R., Scarsi, R., and Barker, P. S.; The Preeordial
' ElectroCardiogiaih, Am. Heaht d. 27; 10, 1944.

. 2 . Roth, G. M.,‘and Kvale, "W. F..; A Tentative Te.st for the Diagnoshs of Pheocdiroinoeyloma,
J.,Lab, & Clin. Med. 30: .3(50, 1045.

- 3. Wood,' F: G., Wolferth, C.,C., and Bellet, ,S.: Infarction of tlie Lateral Wall of the Left
Ventricle-: Electrocardiographic Cliaracteri.stics, A.v. Heakt J. 16: ?.S7, 19.3S,
4..Thpnison, il. tv., and Feil, H.: Infarction of the J.ateral Wall of the Left Ventricle.
Pathologic and Eleetroeardiogi’uyduc Study, Ain. .1. M. Sc. 207: 5SS, 1944.

: . 5. Bosco,. G. ,A.: Sindroine Coronario Lateral, Buenos Aire,s, 1943, linprenta Feriari linos.
6. Wilson^ F, i!^.: ' Diseases of the Coronary Arterie.s and Cardiac Pain, Edited liy Eoliert
Levy,' New Vork, 1936, The Macmillan Company, p. 281.

V Rosenbflum, F, F,, .Tolinston, F. D., and Alzamora, V, AC: Persistent Displacement of the.

c RS-t Segment in a Ca.se of Meta.'itatic Tumor of the Heart, Am. Heart J. 27: (507,

V .. y,-T944A _

...S., Rosenbaum, F. ir., and Wilson, F. N.: "Unpublished observations.

'in' 3^*crsdnal communication to F. N. AAMson.

. F-, Myers, G. B. : Personal communication to F. F. Ro.senbaum. ,

j N., Ro.senbauni, F. F,, and Johmstou, F. D.:- The Interpretation of the A^en-

' ' tncul^ Complex of the Electrocardiogram, Advances in Internal Aledicino, TI,

New V6rk, Interseience Publishing Co. In press.

TJIE DB:\rONSTRATION OP TENTKICULAR SEPTAL DEFECT BY
I^IEANS OP RIGHT HEART CATHETERIZATION

Ei.eakor deP. Baldwin, M.D., Lucille V. ^Mooke, Jil.D., and
Robert P. Noble, j\LD.

New York, N. Y,

^\Lth the Technical Assistance op
j\IlCHAELEEN PaTTERSON, B.A., AND DoRIS ]\I. IIaRNSBERGER, B.S.

I SOLATED vcnlrienlar defects arc not mieomnion. jMande Abhott^ listed 50
pure A'ontrienlar defects in her series of 3,000 congenital cardiac lesions.
Tlie clinical diagnosis of this condition has been entirely dependent upon the
presence of the pathognomonic Roger mni-miir,- a localized loud blowing systolic
murmur hoard best just to the left of the mid-si ernum and often accompanied
by a palpable thrill. Presumably the size of the defect is in inverse proportion
to the loudness of the murmur. An associated cardiac enlargement may be
present. The electrocardiogram is frequently normal, although right axis
deviation and a prolongation of the aurieuloventricular conduction time are not
uncommon. Since the shunt is arteriovenous, cyanosis is not present, except
I’arely as a terminal manifestation. Therefore, many ventricular septal defects
arc not recognized during life but arc found only at necropsy.

The development of a safe and relatively simple technique for the
catheterization of the right heart in man® presents a new diagnostic aid
admirably adapted for the detection of this particular congenital defect. Follow-
ing the introduction of a catheter into the right heart, samples of blood may
be withdrawn from various known areas by determining the position of the tip
of the catheter by fluoroscopy. The presence of an arteriovenous shunt may
then be demonstrated by the comparison of the respiratory gas contents of
these blood samples with one another and with samifles of arterial blood.
Further information on the hemodynamics may be obtained by qonneeting the
intraeardiac catheter to a recording type of manometer, such as the one de-
scribed by Hamilton" and analyzing the resultant pressure tracings. Fiual-
iy> by direct obsei'vation of the movements of the catheter within the
right heart, useful impressions as to the size, shape, and location of the
chambers of the heart may lie acquired which supplement the information ob-
tained from the routine x-ray and fluoroscopic studies. In such a study, however,
two prei’equisites must be met which limit it's usefulness in children; (1) The
peripheral venous system must be sufficiently developed to allow the easy passage
and subsequent manipulation of at .least a No. S, preferably a No. 9 catheter

From the Departments of Aleflicine and Physiology of the College of Physicians and
Surgeons, Colmnbia University, and the Presbyterian Hospital.

Received for publication Nov. 19, 1943.

152

^ ^ ^ KIGHT HJ2AET CATHETERISATION 153 , •

into the median basilic' vein, and (2) enough passive cooperation of the subject;
must be assured ;to maintain a relatively steadjr physiologic state throughout the '
procedure, since it, is quite obvious that the circulation will vary enormously
from minute to minute in an apprehensive, restless, and uncomfortable subject.*

. Heraodjmamic studies made upon two subjects with congestive -circulatory
failure of obscure etiolo^^ vdll be presented in this report. A ventricular septal
defect was demonstrated in both eases.

PROCEDURE

The subject was brought to the laboratoiy in the morning under basal
conditions. He was given 30 mg. of phenobarbital by mouth just before leaving
the ward. The radiopaque catheter was passed through the median basilic vein
into the thorax under fluoroscopic vision, and the tip was manipulated into the
desired position:^ Blood samples were withdravm under oil; a rigid air-free
technique was obseiwed. Pressure recordings, were made in both the right
auricle and ventricle. Simultaneous blood samples were taken from the ven-
tricle, and from the femoral artery through an indwelling needle. These samples
were immediately analyzed for their oxygen and carbon dioxide content in a
Van Slyke manometric apparatus.® In one ease in which the expired air was
collected, aliquots of this air were analyzed for their oxygen and carbon dioxide
content ill a Haldane gas burette. The tracings of the pressures within the right
yentriele, auricle, and peripheral veins were recorded by a Hamilton manometer
which, was. calibrated after each recording.®

- From this series of observations, information was obtained as to the presence
or absence of an arteriovenous shunt, the peripheral blood flow, and the pressure
gradient between the peripheral veins, the riglit auricle, and the right ventricle.

. The demonstration of arterialization of the right ventricular blood is proof
of . an,, interventricular arteriovenous shunt which cannot be questioned if
arterial blood is vuthdrawn from the catheter. Except in the presence of an
. additional tricuspid insufficiency, in which condition the auricular as weU as the
’ ventricular blood will be arterialized, a ventricular septal defect can be detected
. by a significant difference between the respiratory gas content of the auricular

• ' as compared .with the ventricular blood samples. It is, therefore, of importance
, to .determine .what degree of difference may be considered to be significant,

V %ead and his co-workers' have reported that, in three subjects, blood taken from
. the auricle in the region of the tricuspid valve was found to have a very low
' oxygen content compared with samples taken from the right ventricle or other
^ of .the auricle. They concluded that the catheter had entered the
■ . cdrbfiary sinus or an aberrant hepatic vein. Cournand et al.,® on the other hand,

: bave^ s^^ that, the oxygen content of blood taken successively from the right

• . .Aehtricle and auricle close! to the tricuspid valve varied 0.3 volume per cent or
/ less in 19 of 22 subjects, and that in only one subject was the difference greater
, - than T voffi^ per, cent. Thus, a variation of oxygen content of more than 2

‘Since this article was written, Cournand and his group at Bellevue Hospital have studied
young children between. 2y, and 6 years of agre with various congenital heart defects,
^hjg avertln as a basal anestheUc and Introducing a No. 7 catheter into the heart through the
y^pnenous vein; exposed, at the femoral area under local anesthesia.

154 .

AMERICAN HEART JOURNAL

volumes per cent between the venti-ieulai* and auricular samples may lie con-
sidered a significant difference denoting an abnormal communication. Since
the carbon dioxide content of the mixed venous blood tends to vary considerably
from minute to- minute with any slight respiratory or circulatory change, varia-
tions between the carbon dioxide content of the several samples are confirmatoiy
but not reliable evidence of an abnormal shunt. Furthermore, if the subject
under study is in severe right-sided cardiac failure, a functional tricuspid
insufficiency must be suspected and looked for, and, if found to be present, it
must enter into the evaluation of the data.

Indhe absence of a tricuspid insufficiency or an abnormal shunt, the oxygen
content difference betiveen the arterial and mixed venous blood within either the
auricle or ventricle is a measure of the systemic blood fiow. In the normal
resting individual this difference is 4.5 ± 0.7 volumes per cent, but in congestive
failure or shock it may be increased to as high a value as 16 volumes per cent,®’ ®
and, conversely, during anxiety, anemia, or fever, to as low as 2.5 volumes per
cent.^”’^^ If the total oxygen consumption per minute is Icnown during the
period of blood sampling, tlie systemic blood flow may be calculated, using the
simple Fick principle :

Systemic blood flow/min. - Oxygen iotake ml, per minute

Artei'ial Oj vol. % - venous O, vol, %

Since the volume of blood flovdng through the ventricular septal defect is un-
known, the pulmonary blood flow obviously cannot be calculated in the presence
of this condition, unless samples are taken in the pulmonary ai'tery.

The analysis of the pressure tracings is primarily dependent upon an unob-
structed manometrie system. It is often of great value to Icnow the pressure
changes at the site of the blood sampling. For example, if the ventricular blood
is identical "svith that dravm from the femoral camiula, a comparison of the
pressure tracings will determine whether or not the catheter tip has penetrated
from the right into the left ventricle through the defect. Furthermore, an
auricular pressure tracing is the most accurate means for the detection of a
tricuspid insufficiency.®

OBSERVATIONS ON TWO PATIENTS

With this preliminary discussion of tlie interpretation of the hemodynamic
observations made possible by right heart catheterization, the ease reports and
cardiac catheterization studies of two subjects with A’entricular septal defects will
be presented.

Case 1.— A. S., a 20-year-old single giid of Italian parentage, gave a history of a fall at
the age of 7 years in whifeh she struck her epigastrium against a step. Following this accident
she was admitted for abdominal swelling to another hospital, where a diagnosis of rheumatic
heart disease was made. After four mouths tho abdominal swelling subsided and she was
symptom-free until the age of 15 years, at wliich time swelling of her anides was followed
by enlargement of her abdomen. "For the six months preceding admission to the Presbyterian
Hospital, her edema did not respond to treatment. Pliysical examination disclosed a poorly
developed, pale adolescent girl appearing much younger than her chronological age, with a
greatly distended abdomen. Theie were distention and pulsation of the jugular veins. The
lips and nail beds were slightly cyanotic'. The heart was enlarged more to the right thaw to.

155

. BALDWIN ET AL.: BIGHT HEART CATHETERIZATION

tJie left. Over the pulmonar}' conus there was marked pulsation, a systolic murmur transmitted
to the clavicular area, and a diastolic murmur transmitted to the apex. There was a loud
systolic murmur over the apex and tricuspid area. The pulmonic second sound was louder
than the aortic. The abdominal wall was edematous and an obmous fluid wave could be
demonstrated. Pitting edema of the sacrum, shins, and anldes was present. On admission,,
tlie venous pressure was 240 mm. of Avater. Serum proteins were 6,1 6m,, albumin, 4.4 per
cent, and globulin, 1,7 per cent. Other laboratoiy findings were noncontributory. Fluoroscppy
of the chest revealed moderate enlargement of the heart with good pulsation at tlie left and
only transmitted pulsation at the right border,. After ingestion of barium, a posterior dis-
placement of the esophagus Avas noted. The electrocardiogram disclosed a left-axis deviation
and a P-B interA'al of '0.27 second. Clinically, she AA’as considered at this time to have an ad-
hesive pericarditis associated Avith possible chronic rheumatic vah-ular disease. The possi-
bility of a congenital cardiac lesion AA'as suggested by one examiner.

The hemodynamic, studies Avere carried out on the ninth day following her hospitalization,
after diuresis had brought about a 14-pound weight loss.

Eig. 1. — ^Roentgenogram of the thorax in Case 1. A. S.

Procedure (Figsl 1 and 2; Tables I and II). — The catheter passed readil>
into the right auricle, which appeared to be neither dilated nor enlarged, and eas-
ily, slipped through the tricuspid valve into a markedly enlarged right ventricle.
Simultaneous blood samples taken from the right ventricle and femoral arteiy
disclosed .almost identical values for the respiratory gas contents: a carbon
.dioxide content of 50.5 volumes per cent and an oxygen content of 15.6 volumes
per ceut in the ventricular blood, arid a carbon dioxide conteht of 50 volumes
/pel ceiit and an oxygen content of 15.8 volumes per cent in the femoral arterial
, jdeoi. T^^ a completely unexpected occurrence, which Avas iiositive proof

AJIEKICAN

;, I' BLOOD ■ GAS MEAStmEUENTk: ; ,. ... . _ .

rca.e 11. ftmale, 80 ?eaiB oW, °^';;:::!L_,, ^IS======«

^_____^^ OXYHEMO- . _ -GLOBIN

11:21 A.M
12:50, P.M.

I.OCATION' OP
I "catheter TIP ■
"^Ppsterior^ig^t ven-
' tricle ‘

remora! caffliula
Anterior rigiit A’o’i'
'tricle , .

Biglit auricle at tri-
cuspid,

■ Eiglit auricle at
• l^vel of third, nb
Right auricle at 4 cm
' • higher

OXYHEMO-
‘ OLOBIN ,

, CONTENT
(VOLS. %)

15A

“l--

pressure
' (MM. HG)

^ 40/10“

■ oxyhemo-
globin •

SATURATION
' (%)
90.0

15.6

14.4

112/72

40/10

90.8

83.2

82.5

00.8

02.5

jlace

sv-ere.

tt- Biooa P»®s™a

TABLE II. E^O”. , . ^ „iiii„etera ol rrnrm)

■pmaPHERAL ^

pressures
. Systolic
Diastolic
hleau -.

; Pulse

[Case 1 ], pressures

5

^■riOTT . 1

■ right

1 auricle

1 femokal I

. autbky J

1 . - yentriclb
43^33““

L, .

27-23

/;■ ^ ^ : BALDWIN ETAL.; RIGHT ; HEART CATHETERIZATION , ,157

of a septal' defect. While awaiting the. afore-mentioned determinations, simultaner
, ous femoral and right ventricular pressure tracings were recorded without chang-
. ing the position of the catheter. It was very evident from these pressure tracings
that the catheter tip had not entered the left ventricle, since the femoral arterial
pressure was 112/72 and the right ventricular pressure was 40/10. Wlien the
results of the blood gas analysis were known, the catheter was widely manipu-
lated. The right ventricle was . obseiwed to extend from about 1, cm. below ^
: the steinum (Fig. 2) to mthin a centimeter or two of the vertebral column. A
second ventricular sample taken from the anterior area of the right ventricle
disclosed a carbon dioxide content of 50.8 volumes per cent and an oxygen content
of 14.6 volumes per cent, thus sliowing an admixture of mixed venous blood.

: ■ , . Fig. 3. — ^A, Simultaneous right ventricular and femoral pressure curves, taken with th^'

catheter in the position shown in Fig. 2. B, Auricular pressure cur\'e at the tricuspid valw.
■,C, Auricular pressure cuiwe taken at the level of the second anterior intercostal space, p.
Pressure curve taken in the hrachial vein. E, Pressure curve taken in external jugular vein
■ '.two weeks later.

. ' -The pressure at this i^oint were identical mth the previous ones (Fig.

3, A). . Upon withdrawing the catheter from the right ventricle while taking
continuous pressure tracing, a blood sample was talmn close to the tricuspid
■ where the pressure curve first changed from the ventricular to the

, auricular pattern. The respiratory gas content of this sample closely checked
vith tile second ventricular sample (a carbon dioxide content of 51.2 volumes
' per. cent and an oxygen content of 14.3 volumes per cent). The auricular

158

AJIEUICAN ilEAUT JOURNAL

pressure tracings at this point sliowed evidence of tricxrspid insufficiency, i.e.,
marked abnormal systolic increase in pressure. Unfortunately, these tracings
were not timed by cither an electrocardiogram or a femoral tracing (Pig.
3, B and C). Two further auricular blood samples were taken from the right
auricle at about the level of the fourth aTiterior rib and second anterior inter-
costal space. The pi'e.ssurc fracings at thc.s'c points were similar to those obtained
from the tricuspid area but the rcspiratoiy gas contents, which cheeked one an-
other, disclosed considcrablj' more cai'bon dioxide (52.‘lr volumes per cent) and
less oxygen (10.4 volumes per cent) than the one taken at the tricuspid valve.
Pressure tracings taken in the brachial vein continued to .show retrograde pulsa-
tions associated with tricus])id insufficiency, although ten days later, following
a 25-pound diuresis, no evidence of tricuspid insulTicicney could be found on an
external jugular tracing (Pig. 3, 1) and 7f).

Swmnnry . — ^Thc practically identical respiratoiA- gas contents of the arterial
' and right vcnti-ieular blood sajuplcs prove the presence of a ventricular septal
defect. A functional trieusi)id insufficiency and right ventricular hypeilension
were demonstrated by the iiressure tracings, the former being substantiated by
the arterial contamination of the auricular blood sample taken at the tricuspid
valve. In view of the extensive tricuspid insufficiency, no c.stimation of the
peripheral blood flow was possible. The diminution of the pressure gradient
between the peripheral and central venous pre.ssures was an additional reflection
■ of the extensive eardio-eirculatory failure.

Case 2. — T. P,, a IG-ycar-old Negro schoolboy complained of a painless gradual enlarge-
ment of Ins abdomen for six montbs prior to his ndmission to the hospital. Ho had continued
to participate in his usual activities, including basketball, witiiout discomfort. He denied
dy.spnca, orthopnea, cough, or chest pain. The past history was ontirelj- negative except for
pneumonia at 9 and gonorrhea at 14 years of age. On admission, he was observed to be a wcll-
dev'cloped and well-nourished boj-. lie could lie flat without discomfort. The heart ^\as slight-
ly enlarged both to the right and to the left. No thrill was palpable. The heart sounds were
of good quality; P, was loud and snapping. A short, lu'gh-pitched, systolic murmur was heard
slightly above the apex but was not transmitted. The liver was palpable 4 fingcrbioadths be-
low the costal margin and was very .«lightly tender. The spleen was palpable .1 fingerbreadtlis
below the left costal margin. Neither ascites nor peripheral edema was present. Clubbing
of the fingers or cyanosis wa.s not observed. Tlie laboratory findings were essentially negative;
the blood count, orytlnocyto sodimentntiou rate, and serum proteins were normal. The electro-
cardiogram showed a right-axi.s deviation, and a P-P interval of 0.20 second, T, and T, were
isooloetric, T^ showed low voltage, and T,,- was large. X-ray (Fig- 4) and fluoroscopic exam-
ination revealed the heart to bo slightly enlarged to the right and to the left, with enlarge-
ment of the right ventricle and pulmonary conus, and a small aorta. The pulsations were
good, except along the upper right border. The left auricle was markedly enlarged, dis-
placing the esophagus po.stcriorly. There was no hilar dance. The roentgenogram was
normal; pulsations were observed in all the visualized portions of the heart. The venous
pressure w-as 347 mm. of saline, the circulation time was 15 seconds, and the vital capacity
was 3,500 cubic centimeters. The clinical opinion in this case was divided between an
interauricular septal defect and a constrictive pericarditis.

Procedure . — The catheter was passed without difficulty into the right
auricle. This chamber did not appear to be enlarged. Due to the suspicion
that an interauricular septal defect might lie present, blood samples 'were

: ^ , bALD\VIN ET AE. : RIGHT HEART CATHETERIZATION lo9

tateii from the superior vena cava, from the hepatic vein, and from the nght
, auricle before dhe catheter was slipped into the right ventricle. Tins eliamber
Was markedly dilated. Simultaneous right ventricular and lemoral arterial
blood samples were withdrawn during the eolleetion of expired air. Although
the patient was hyperventilating moderately, his pulse remained constant.
Manometric tracings were taken of the right ventricular, and, upon wthdrawal,
of the auricular pressures. A final auricular blood sample was withdrawn two
and one-half hoiirs.after the first sample.. The catheter was within the heart two

hours and fifty minutes.

yig.. 4 , — Roentgenogram of the thorax in Case 2.- T. P.

The respiratory gas contents of the various Ifiood samples aud the lijnes ;
and location of sampling are presented hi Table HI. As can he seen, the gas
' contents of the hepatic vein aud right auricular blood checked vein^ closely even
over a period of more than two hours, whereas the blood from the superior vena
cava disclosed considerably more carbon dioxide and less oxygen. A difference
of this magnitude between the gas contents of the superior vena eaval blood aud
the right anricnlar and hepatic blood has not infrequently been observed. The
presence of a small intcrauricular septal defect with the stream of blood flowing
down into the tricuspid and hepatic, vein region might be su.spccted on this data
nlone hut would appear to be unlikely in the presence of a normal-sized auricle
and a normal anricnlar pressure, tracing. Tlic ventricular blood, however,
allowed a marked degree of arterialization, which i.s consistent with the diagno.sis

360

AMERICAN REABT JOUBNAE

Tabli: III. Blood Gas Measurements

(T. P. [Case 2], male, 16 years old, oxyhemoglobin capacity 16.8 volumes per cent)

TIME

LOCATION OF
CATHETER 'TIP

CARBON
DIOXIDE
CONTENT
(VOLS. %)

OXYHEMO-
GLOBIN
CONTENT
[VOLS. %)

PRESSURE
, (MM. HO)

OXYHEMO-

GLOBIN

SATURATION

(%)

9:40 A.M.

Superior vena cava

43,1

9.0

mean 22

53.6

9:45 A.M.

Hepatic vein

41.5

10.9

64.9

9:50 A.M.

Eight auricle

43.2

10.6

mean 22

63.1

10:58 A.M.

Eight ventricle

38.8

13,9

.54/25

82.8

10:58 A.M.

Femoral cannula

38.1

16.6

118/70

98.8

12:. 30 P.M.

Eight auricle '

40.9

11.0

mean 22

65.5

T.VBLE W. Hemodynamic hlEAsuKEMEXTs
(T. P. [Case 2], 16 year.s old; body surface aiea 1.87 M.-)

MEASUREMENTS

1 CONTROL 1

OBSERVED

Ventilation L./min./M.® B. S. A.

4.04 ± 0.64

5.66

. Pulse

66 ± 7.6

86

Oxygen consumption c.c,/min./M.2 B. S. A.

129

Arteriovenous difference vol. %

4.5 ± 0.7

5.7

,, Systemic blood flow L./min./M .2 B. S. A.

3.12 ± 0.4

2.26

Plasma volume c.e./M .2 B. S. A.

1,600

2,370

Table V, Blood Pre.ssure MEA.suREMn.\’rs
(T, P, [Case 2], pressure recoided in millimeters of mercury)

PRESSURES

I FEMORAL

ARTERY

RIGHT j

VENTRICLE

RIGHT

AURICLE

PERIPHERAL

VEIN

■ .Systolic

' 118

54-47

27-25

Diastolic

70

25-20

22-20

Mean

80

22

22

. Pulse .

48

29-27

of a left-to-right arteriovenous shunt and is associated with a marked dilatation
of the chamber of the right ventricle. The pressure tracings showed a high ven-
tricular systolic and diastolic pressure (Table V). Since the auricular tracing
disclosed no evidence of a tricuspid msufficiency or [latent auricular septum, it
was possible to calculate the peripheral blood flow from the mean auricular and
femoral blood oxygen difference (Table IV). That the patient was in a very
steady state is indicated by a constant pulse and the close eheclcs of the carbon
dioxide contents of his auricular blood samples over a period of two and one-hall
hours. The hyperventilation observed during the collection of his expired air
was apparent several daj's later when some respiratory studies were done under
truly basal conditions, and thus it presumably was not induced by the procedure.
His peripheral blood flow was low and there was a loss of pressure gi’adient
between the peripheral and central veins, which findings confirmed the clinical
impression of cardio-circulatory failure. Following these obseiwations, the
patient was digitalized, with a resulting weight loss of 11 pounds. Seven
months later he re-entered the hospital in severe congestive failure with ascites
and marked pitting edema which was improved bj'- bed rest and diuresis.

Sumniary . — The arterialization of the right A^entrieular blood demonstrated
the presence of an interventricular septal defect. The identical respiratory

BALDWIN KT '.Ui. ; RIGHT HEART. CATHETERIZATION IGl ..-

gas;coiiteDts of tlie liepatic vein and the. auricular blood, and the absence of an : '
enlarged right aiifiele practicall}- rule out a -functional auricular septal de’feci:.
The patient -s congestive failure .was reflected bj a low peripherar blood flow,
increased intraventficular' and auiTcular pressures, a loss of pressure gradient
betv:een the peripheral and central veins, and an increased plasma volume. ,

.// . DISCUSSION ' , / .

The marked arterialization of the right ventricular blood of these two sub-
jects is positive ewdence of the presence of an arteriovenous shunt through tlie '
ventricular septum. Wliether or not this defect is the only anomaly present in,
these patients. cannot be stated. In the absence of infection, congestive failure'
in pure yentricular septal' defect is considered unusual. Of Abbott’s 50 ''pore”
cases, only four died of cardiac insuffieienc 3 ^ In the autopsy flies of the Presby-
terian , Hospital, six c^ses are listed as having an isolated ventricular septal de-
fect, in two of which tlie cause of death Avas cardiac insufficienc}’. It is obvious -
that the septal defect was large in both of our patients. Although in the case
of A. S'. (Case 1) the flrst A'entrieular sample must have been taken directly from
the. arterial stream, the second ventricular and Aret auricular samples are prob-
ably more representative of , the mean ventricular mixture, of which approx-
imately 70 per cent must hai’e come from the arterial side. Similarly, the per-
centage of arterial blood in the ventricular sample taken from T. P, (Case 2)
must have been in the neighborhood of 60. It therefore seems logical to conclude
that, the apparent large size of the arteriovenous shunt contributed materially to
the development of cardio-cireulatory failure in these two subjects. Moreover, in
our first case- there was some questions of a pericarditis being present, based upon,
poor, pulsations of the right heart border and calcification in the region of the , ,
right ventricle. Dr. Eobert Le\y considered the possibility of an additional :?
patent ductus arteriosus as contributing to heart failure. It is of interest that ■
in both these patients congestive failure became crippling at the ages of 15 and
16 years, respectively, in view of the fact that Abbott's figures indicate that the
average life expectancy of individuals with a ventricular septal defect is 14iyl>
years.. . ' ' /

Upon routine x-ray and fluoroscopic examination, the esophagus of each of
these patients was considered to be displaced posteriorly by what was in-
■ terpretedhs an enlarged left auricle, but Arith the catheter in place it appeared
; to be the right ventricle. In the first case the catheter tiii Avas obserA-ed to be .
closely adjacent to the vertebral column in one position, as Avell as beneatlfth*'
stemuni anteriorly in ;another (Pig. 2). Thus, in this' subject the right ven- r
. tricle appeared to fill almost the entire anterior posterior xflane of the thoracic
cage. In the second patient an attempt Avas made to pass the catheter into the
pulmonary artery. During tliis imsuccessful attempt the catheter tip Avas seen
to moAm along within the prominence AAdiich formed the left upper heart border,
identifying this to be part of the enlarged right A'cntiicle, These observations
emphasize; the: difhculties of- an attempted inteipietation of the homogenou.s ,
cardiac shadow Avitliout the aid of a contrast medium.

162

AJIERICAN HEART- JOURNAL

The detection of an arteriovenous shunt by this metliod is obviously de-
pendent upon having -a sufficiently large admixture of arterial blood bathing
the tip of the catheter during the eolleetion of the sample to produce a signifi-
cant auricular ventricular oxygen difference. Ob\dously many smaller shunts
can be missed by this method. Since the usual anatonue site for these defects
is at the base of the heart, the tip of the catheter should be directed to that
location for at least one sampling. In smaller septal defects the additional
findings of right ventricular dilatation and/or hypertension would not be
anticipated. But if a bacterial implantation Avere present, a positive blood cul-
ture might be obtained.

SUMMARY

Observations made by means of right heart catheterization upon the hemo-
dynamics of two subjects with congestive failure of obscure etiology are reported.

In both subjects a large ventricular septal defect was demonstrated by the
arterialization of the right ventricular blood.

The authors are greatl}' indebted to Dr. Dickinson W. Richards, Jr., and Dr. Andre
Cournand for their advice and helpful criticism.

REFERENCES

1. Abbott, M. E.: Congenital Heart Disease. Nelson New Loose Leaf Medicine, New
York, 1920, Thos. Nelson & Sons, vol. TV, pp. 207-321.

- 2. White, P. D.: Heart Disease, ed. 3, New York, 1944, The Macmillan Co., p. 296.

3. Cournand, A., Rilej', E. S., Baldwin, E. deF., and Richards, D. W., Jr.: Measurement

of Cardiac Output in Man, J. Clin. Investigation 24: 106, 1945.

4. Hamilton, W. F., Brewer, 6., and Brotiman, I.: Pressure Pulse Contours in an Intact

Animal. I. Analj’tical Description of a New High-Prequencj’ Hj^podermic
Manometer With Illustrative Curves of Simultaneous Arterial and Intracardiac
Pressures, Am. J. Phj'siol. 107: 427, 1934.

5. Peters, J. P., and Van Slj'ke, D. D.: Quantitative Clinical Chemistry, vol. II, Methods,

Baltimore, 1931, Williams & Wilkins Co., p. 324.

'6. a. Cournand, A., Law.son, H. D., Bloomfield, R. A., Breed, E. S., and Baldwin, E. deF.:
Recording of Right Heart Pressures in Man, Proc. Soc. Exper. Biol. & Med. 55:
34, 1944.'

b. Bloomfield, R. A., Lawson, H. D., Breed, E. S., and Cournand, A.: Measurements of
Right Auricular and Ventricular Pressures and Description of Various Patterns
of Intracardiac Tracings in Normal Man and Chest and Cardiocirculatory Disease.
In press.

7. Stead, E. A., Jr., Warren, J. V., Merrill, A. J., and Brannon, E. S.: The Cardiac Output

in Male Subjects as Measured by the Technique of Eight Arterial Catheteriza-
tion. Normal Values With Observations on the Effect of Anxiety and Tilting,
J. Clin. Investigation 24: 326, 1945.

8. Cournand, A., Riley, E. L., Bradley, S. E., Breed, E. S., Noble, E. P., Lawson, H. D.,

Gregerson, M.'l., and Richards, D. W., Jr.: Studies of the Circulation in Clinical
Shock, Surgery 13: 964, 1943.

9. McMichael, -J., and Sharpey-Schafer, E. P.: Action of Intravenous Digoxin in Man,

Quart. J. Mod. 13: 123, 1944.

10. Brannon, E. S., Merrill, A. J., Warren, J. V., and Stead, E. A., Jr.: The Cardiac Out-

put in Patients ' With Chronic Anemia as Measured by the Technique of Eight
Arterial Catheterization, J. Clin. Investigation 24: 332, 1945.

11. Sharpey-Schafer, E. P.: Cardiac Output in Severe Anemia, Clin. Sc. 5: 125, 1944.

A SIMPLIFIED AND MORE STANDARDIZED TECHNIQUE FOE
, RECORDING MULTIPLE PREGORDIAL ELECTROCARDIOGRAMS •

Arthur J. Geiger, M.D., and Jessamine R. Goerner, ]\r.D.

New Haven, Conn.

A lthough the superiority of multiple chest leads to any single precordial
placement is well known to eleetroeardiographers, the majority of lab-
oratories and physicians still fail to take advantage of this fact in routine electro-
cardiography. It is probable that this dilatoriness in adopting a technique of
proved value is attributable to several factors: (1) the recording of multiple
chest leads instead of a single one calls for additional technical time and effort,
(2) the average laboratory technician is probably incapable of selecting cor-
rectly the anatomic sites specified by the American Heart Association for the
six precordial placements,^ and (3) there is still uncertainty and inadequate
information concerning the normal ciiteria for chest’ lead electrocardiograms
obtained from all six precordial placements with the four conventional attach-
ments of the indifferent or distant electrode. This last deficiency would un-
doubtedly be remedied sooner if the retarding influence of the first two factors
named were removed, and then the routine employment of multiple preeordial
derivations would probably be more widety adopted.

In an effort to expedite, simplify, and expand the practice of recording
multiple precordial lead electrocardiograms, we have devised and studied the
procedure described in this paper. Ample preliminaiy tests appear to establish
the procedure as clinically useful and reliable.

, methods and procedure

Instead of identifying each of the precordial lead placements individually
as recommended by the American Heart Association, the technique we employed
requires finding only Positions 1 and 6, both easily identified; Positions 2 through
5 fall arbitrarily at even distances between 1 and 6. This is accomplished by
the use of an elastic electrode belt made of good quality rubber of uniform
elasticity. The belt, which is 3 cm. wide and at least 120 cm. long, is perforated
at intervals of 4 cm. with holes sufficiently large to hold the handles of the six
chest electrodes.* After the patient’s chest has been marked in Position 1
(right sternal margin at fourth intercostal space) and Position 6 (midaxillary
line halfway between tlie axilla and the costal marginf), the belt is applied

Prom the Department of Internal Medicine, Yale University School of Medicine, New
Haven, Conn.

Received for , publication Nov. 23. 1945.

‘Belt and circular electrodes (3 cm. in diameter) supplied by Cambridge Instrument
Company, New York, N. Y.

, tThis point faills within ± 1 cm. of the midaxillary point, reached by "a line drawn from ..
the left sternal margin in the 4th intercostal space to the outer border of tlie apex beat (or
to a point of junction of the midclavicular line and the 5th intercostal space) and continued
around the left side of the chest," as specified by the American Heart Association.-

; ^ ^ 163

164 / ' , , . AMEHIGAK HKAllT, JOURNAL ‘

SO iiiat the. fiiEt electrode overlies Position 1 and the sixth electrode overlies:
Position 6; the four intermedialie electrodes wiE then lie at even distances be-
tween the first and sixth as determined by; the stretch of the belt. Electrode
jeUy is applied to the surface of each electrode. by lifting one. edge, and satis-'.,
factory contact is obtained by twirling the electrode against the sldn.' In
recording the six chest leads the, preeordial lead hare is connected vith each of
the electrodes in turn, or a six-station switching device® may be interposed.
Pig. 1 illustrates the electrode belt and SAviteh.

. . ■ , JTigr. 1.— Left oMlque view of the electrofle belt In .use. The switchbox, A, Is an optional
"convenience for rapid recording from' each of the six precordial positions; if the switchbox is
not used, the chest lead wire, B, from the electrocardiograph is simply connected In succession
with each of the six precordial electrodes. _

. Whether one follows the precordial placements recommended by the Ameri-
. can Heart Association or utilizes the belt teehniqire described, Positions 1 and 6
tviU, be identical) but Positions 2 through 5 may differ moderately between the.
definitive official placements and the more arbitrary placements imposed by tlie, ,
belt.* Pig. 2 illustrates the differences in the electrode positions of the two .

. techniques on the.thorax of a man of intermediate size arrd build. * .

■ The validity of the belt technique may be assessed, in part, by iroting bow
closely the electrocardiograms obtained by the belt placements of the electrodes, .
i-esemble the tracings obtained' by the, definitive anatomic placements. Such a .
study was undertalren on nor-mal subjects arrd oir a group of patients with cardiac
arrd electrocardiographic abnoraialities. The normal group included subjects of. ,
both sexes and of all body types from the asthenic, whose vertical hearts were '

‘Obtained from Sanborn Company, Cambridge, Mass.

; GEIGER .AKD> GOERNElt:

]\IULTIPLE PRECORDIAL ELECTROCARDIOGRAMS

165 '

largely ; retrosternal, to the extremely obese and lijTjersthenic with relatively-
horizontal position of the heart. All electrocardiograms were obtained with the '
subject reclining and with the, trank elevated to an angle of 45 degrees. The six
precordial electrocardiograms were recorded by both the conventional and the -
belt techniques, •with the indifferent electrode attached successively to the right
arm, left arm, left leg, and to a central terminal of 5,000 olims resistance.’^ The
galvanometer was adjusted to a sensitivity of 1 cm. per millivolt. The two
series of twenty-four electrocardiograms each, obtained by the two techniques,
were then carefully compared.

Pig. 2.-— Tho blackened circles mark the six precordlal electrode positions as defined by
the American Heart Association: the numerals indicate the positions assumed by the electrodes
with the elastic bolt technique. The subject was a man of intennediate build whose electro-
cardiograms -obtained by the two techniques are compared in Experiment 1 of Table I,

RESULTS

; I. Normal Subjects . — Thirty iiomal young adults (fifteen men and fifteen
women) were selected as experimental subjects. Two parallel series of chest
lead electrocardiograms were made upon each by the conventional and the belt
techniques described; the results were carefully compared and the differences
w'ere tabulated.

Auricular deflections are usually poorly represented in precordial leads as /
compared with limb leads ; the slight differences that occurred occasionally in P
waves of the two series were considered insignificant. For the purposes of tliis
study attention was focused on the details of the ventricular complexes. The :
dissimilarities noted are summarized for the male and female subjects in Tables
I and II; where, ^differences existed the actual amplitudes of the, deflections
are stated in millimeters, with the value by the conventional technique to the
left of the colon ( :) and the value by the belt technique to the right. ,

’ It.may be seen from the tabulations that only exceedingly slight or. imper-
ceptible’ differences were noted between the twenty-four pairs of tracings in /
eleven of the subjects {6-rade of Similarity: A). Pigs. 3A and ZB illustrate
the /remarkable similarity of the comparable electrocardiograms in a.-repr-e-
sent'atwe subject of this group, •

•These four peripheral attachments were easily and quickly made through the use of . a
suitably designed switching device made for us by Sanborn Company, Cambridge, Maias,

166

AIMERIGAN HEART JOURNAf

In sixteen eases there were moderate differences, nsually in the relative
amplitudes o£ R and S, and occasionalh'- in tlic amplitude of T {Grade, of
Similarity: B). Pigs. iA and 4Ji illustrate the tracings in a tj'|)ieal ease of
this group. '

In three eases the records were cla.ssified Grade of Similarity; 0, because
either Q or S was present in some of the tracings by one technique and ab-sent
by the other, or because T was oppositely directed in one or more tracings of
the, two parallel series. Inspection of tlic data in Tal)lcs I and II will reveal

Fie. SA.

Figs. 3A and 3iS. — ^Normal male subject (N. J.). In this' and the figures. that follow.
OR, OJj, OF, and OV refer to the placements of the indifferent (distant) electrode on the. right
arm, left arm. left leg, and a central terminal of 5,000 ohms resistance, respectively. The
arable numerals 1 to 6 refer to the precordial positions of the exploring (near) electrode; the '
suffixes a and h indicate electrocardiograms obtained by the conventional and belt techniques, '
respectively (see text for details).

GEIGER AND GOERNER: MULTIPLE PRECORDIAL ELECTROCARDIOGRAMS 167

tliat. Q-, >S-, and T-\vave differences in tliis group concerned only deflections of
■very siiiaii amplitude. Figs. 5^ and 57i illustrate the electrocardiographic dif-
ferences in one of these tliree most dissimilar cases.

The QRS patterns were sliglitly more variable in the female series than in
the male, yet without apparent correlation Avitli body build. Also, several of the
women consistently yielded tracings with more or less serious artifact in the

a

1 -..V.

l-.-;; i

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r : •: ■;.! ■ T ; i '.:/ '■ 'I '■I'' * 1

r. . 'A... l ^ s : ■■■■■ ' ■■ ■ ■ . 1

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r' . , f-

ji i.-j-. •* ■■■ ■ •' ;"'■■■ ''

^i," ■.’! \ ,« ,*. 51 . i*i., 4 . ••* 4 iSa j"; •'/t*

i j-'' ,* *' J‘- • * •• •• • ?*■■■!■. i:'.:-*.

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?L.:‘ *.5.. ii;.i»j:. i ; '* '•■•I \I* !:.!•*!•* , i li: ,*.* •*’!,*.'* I’ iL. ’

i JtiIi •i.!!i***l**;«tinl*'***“, '!*,’*■■ - (,1.****, •*

iWf'**'-?.* .'.'J'.;;.'? i K.-.. *.'**'*i*--‘ “!■ ‘ f !' *■ ' L' • . '■ *■" i

iSi;-;- . p;; ‘.i 'J 'f-i' b; ::i; ■ -ihi'-;- .'bi;' I :;'Vi ■

fev; ivyi:.';|yv'; TV j;! Ai,y L i,:;:\ ; j.iii.v'L;;;:'' ■■:■;■■; L- i ' ia:

v: :;:-. ...i. Ij.i'-'. J!", -.'i • ■/; i-j:’*'.'.-."; ■’i"'' '':v '■ = ;’ :■■■■>■

d

ill!.:.:, 'll.;.... I.-;

si?:: tI; ■vv'j' i!-:

... . j;'" i.-

Hm* I • ■ i I V ■' *4 1 • ■ ■ tMViifI'

= glPPPPPSP

.!f VJ.

Pig. 3B. — (.For legend see Fig. SA.)

FIs. ,44>

Figs. 4A ana iB.—Normal male subject (H. H.).

this suggested that imperceptible slipping of the electrodes in the region of the
female breast' was the cause of the difficulty. ■ .

It was interesting to observe that relative largeness of deflections in com-
parable tracings wus not a uniform characteristic of eithez* technique. Thus, as
may be seen in Tables I and II, a given deflection was sometimes of greater

‘ ' . ' '-N

GEIGKR AND GOERNER:^ MULTU^LE PRECORDIAL ELECTROCARDIOGRAMS,, Iby

amplitude witli one technique than with the otlier in a given subject/ while in
another subject tlie same technique yielded relatively smaller deflections ; and iii
some instances relative largeness of given deflections was manifested alternately
by the two techniques, not only between different electrode positions but also
vdth the same position on changing from one to another of the four indifferent
peripheral electrode attachments.

FI&. 45. — (For legend see Fig. ^A,)

It is apparent from the representative illustrations and from the details
giveh in Tables I and II on all thirty normal subjects-that in no case were the
differences between the electrocardiograms obtained by the two techniques of
such nature or. degree as to be clinically significant.

170

AMKHICAK IIKAKT JOUHNAL

Tliat the j'ecordcd dissiniilaritieSj though relativel.y minor, were not neces-
sarily attrilnitahle to positional varialions of the chest electrodes hetween the
conventional and. the licit placements was suggested by the observation that
oven the tracings obtained from the first and from tlio sixth positions, whose
plaeemciils were identical in the two techniques, showed occasional difTerences.

, C R

CL

CV

GEIGER AND GOERNKR: MULTIPLE PRECORDIAL ELECTROC^UIDIOGRAMS 171

Tables I and II ) ; (2) the grades of difference between the members of a pair
of tracings obtained by the two techniques on any of the normal group were no
greater than the variations noted in the series of twenty records on the same
subject employing the conventiow.il technique alone (compare Table IVA with
Tables I and II) ; (3) there was actually greater uniformity in the series of
twenty electrocardiograms obtained on the same subject by the belt technique
than by the conventional selective placement of the chest electrode (Table IVjB).

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■ nieai origin. Vaiiations in the height of the diaphragm, vhth resultant altera-

Table I, Dipfebenoes Between Pkecokdial ELECTROOAtoioGRAMs Obtained bt Conventional and Belt Techniques in Fifteen

Normal Male Subjects

(Amplitudes of deflections with, conventional and belt techniques appear to left and right of colon, respectively.)

172

AMERICAN HEART JOURNAL

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GEIGER AND GOERNER: MULTIPLE PRECORDIAL ELECTROCARDIOGRAMS 179

tioiis in the position of the heart in relation to the overlying electrodes^ prob-
ably explain many of the differences noted. . J\Ioreover, the belt technique seemed
to permit more uniform reproduction of serial precordial electrocardiograms in
the same subject from day to day. '

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Fig. 6B . — (For leyend see Fig. GA.)

II. Cardiac Gases.— A small number of exploratory observations were car-
ried out in patients witli heart disea.se and abnormal electrocardiograms in. order
to observe again how eloselj^ the tracings obtained by the two techniques re-
sembled each other. The cases selected were examples of those that exhibit
gross and characteristic almormalities of tlie QRS complex, ES-T segment, and
T waves;, they included examples of right and left bundle branch block, left
ventricular h^mertrophy and strain, and acute myocardial infarction. The re-

AMERICAN HEART JOURNAL

si are best presented by the actual electroeardiogracs obtained. by each tech-

nique (Figs. 6 to 10). on in these pathologic cases, the differ-

.eneesl'lh" — \-\he two techniques were ndnor and, in our

nninioii. clinicaUy insignificant.

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Figs. 7-A and 7S , — Patient T. ■» 'branch block- ■

GliGER AND GOERNER MULTIPLE PRECORDIAL ELECTROCARDIOGRAMS 181

- ■ COMMENT . ' i V ^

Six-positional jirecordial electrocardiograms can be recorded more : easily. V
-and efficiently bj* the application to the thorax of an elastic belt eariying six ; '
electrodes than by the selective anatomic placement of the cliest electrodes for ^ , .
each of the six officially designated preeordial positions. Moreover, there is -
evidence that the precordial belt technique permits fully as good, or better, ' '
duplication of results in repetitive examinations than does the conventional. ,
technique. ,

Figr. 7B» — {For legend see Fig^ ,7A,) ^

I

186 ■

A:\U!;uiCA>r hkart journaIv

In applying the electrode belt the te'ehnician need find only two easily
identified anatomic landmarks (Positions I and 6). Witli the conventional
technique it is necessary to idenliJy in addition the other four eleetrode positions
including the important and elusive Position 4, in relation to which Positions 3, 5,
and 6 are located. Position 4 i.s officially defined ’ as the outer border of the apex

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Figs. lOA anfl lOB. — Patient S. B., with ac\ite inyocarCial infarction, posterior-hasal location.

beat (often undeterminable, especially in chests of emiDhysematous or obese
subjects), or as the point of junction of the fifth intercostal space and the left
midclartcular line (not readily determinable with accuracy). The imputed im-
portance of Position 4 in itself and as a reference point for sevei-al other posi-

■ , GEIGER. AND GOEltNKR ; MULTIPLE P11EC0RDL4L ELECTROCARDIOGKAMb <

tions, and the improbability that most teelmicians can reliably identify it, arc
cogent theoretical objections to the conventional procedure.

One may even question the logic of . attempting to place the preeordial
electrodes in fixed positional relationships to the For example,- in .the

electrocardiographic study of cardiac eiilargeinent and displacement, , and in
the differentiation of right and left bundle branch block by preeordial lead ex-

"cl?:

C;k

nr

Fig. lOB. — (For legend see Fig. 10 A.)

ploration, it would seem that anatomic variations in the total heart mass (and
in the right and left ventricular components) would be more reliably revealed,
by adhering to relatively fixed positions of the electrodes on chest wall:
The further discussion of this point is not particularly relevaht to .the .present
study and will be the subject of a later report. . ' , \ '

Inasmuch as anolther; though minor, puiposc of - the preeordial belt tech-
nique was to shorten the time required tou:ecord multiple preeordiaMead electro-

188

AMERICAN HEART JOURNAL

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‘Denotes features In which there was less variation with the belt technique than with the other.

GEIGER AND GOERNER : MULTH’LE PRECORDIAL, ELECTROCARDIOGRAMS 189

cardiograms, the t\TO techniques were timed during recordings of the CPi _5 series.
With the aid of the precordial belt,, the recording was accomplished in approx-
imatelj’’ two-thirds of the time required for the conventional procedure.

It is hoped that the advantages of the technique described will encourage
freer and wider routine recording of multiple precordiab electrocardiograms, and
that through such, greater experience the loiowledge and clinical value of this
imiiortant aspect of electrocardiography will develop more rapidly and along
more uniform lines. , ,

SUMMARY

1. A simple, rapid, and clinically valid technique is described for recording
multiple precordial lead electrocardiograms.

2. The technique employs an clastic belt carrying six precordial electrodes ;
for the placement of these only the' fiist and sixth precordial positions need
be defined.

3. With this i^rocedure the precordial electrode placements are distributed
equidistantlj’ over the precordium. Certain theoretical advantages of such place-
ments that are in fixed relation to the thorax, rather than to the heart, are dis-
cussed biiefly.

REFERENCES

1. a. Standardization of Precordial Leads; Joint Pecommendations of the American Heart
Association and the Uardiac Society of Great Britain and Ireland, Am. Heart J".
15: 107, 1938.

b. Supplementary Report, Am. Heart J. 15: 235, 1938.

INFLUENCE OF VARIATIONS IN ATMOSPHERIC TEMPERATURE
AND HUMIDITY. ON THE RATES 01^’ WATER AND HEAT
LOSS PROM THE RESPIRATORY TRACT OP PATIENTS
WITH CONGESTIVE HEART FAILURE LIVING
IN A SUBTROPICAL CI.BIATE

G. E. Burch, M.DA
New Orleans, Tja.

S tudies oI the mtes of water and lieat loss from the rc.sjiiratory ti‘act of
patients with eongestive licart failure were rc]:iortcd ])reviouslyd These
observations Avere limited entirely to comfortable atmospheric conditions. Since
man finds himself, both during health and disea.se. in atmospheric condition.s
of great variations, it w'as considered of interest to Icnow how certain variations
in atmospheric temperature and humidity influence the rates of water and heal
loss from the respiratory tract of patients suffering with congest ivc heart failure.
This is of particular importance when it is realized that extreme variations in
environmental conditions will precipitate congestive heart failure.'' = It wa.s
noted in these two studies that a hot and humid environment would precipitate
an acute attack of cardiac astluna as.soeiated with ai)prehension and panic. A
Icnowledge of the effects of such an eindronment on the rates of water and heat
loss wmuld aid in understanding the influences of a hot and warm atmosphere
upon the management of congestive heart failure.

JIETUODS AND MATERIALS

The methods employed for the measurement of the rates of water and heat
loss have been described.^’ ^ The subjects consisted of thirteen patients Avith
moderate Functional Class IV"* congestiA^e heart failure of both right and left
ventricular types. These jiatients Averc all bedridden and under essentially the
same standard form of treatment for their uncomplicated heart failure. They
Avere transported from their hospital bed to the laboratory for study. They
I’ested in the laboratory at least thirty minutes before any observations Avere
commenced and remained comfortably seated in a eliair throughout the study.
They Avere clothed in an ordinary tyiic of cotton hospital gOAA'u and eoA'ered Avith
a cotton sheet from the Avaist doAvn.

The patients Avere first studied in a cool foggy atmosphere: the mean tem-
perature Avas 13.9° C. (extremes, 10.5 and 16.1) and the mean relative humidity
Avas 94 per cent (extremes, 89 and 100). The room conditions AA'cre then changed
to make it comfortable: the mean temperature Avas raised to 20.3° C. (extremes,
19.7 and 21.1) and relative humidity AAms loAvered to 58 per cent (extremes, 54

Aided by a grant from the Rockefeller Foundation and tbe Helis Institute for Medical

Research. '

Received for publication Dec. 12, 1945.

♦From the Department of Medicine, Tulane Medical School, and the Charity Hospital,
New Orleans.

390

burgh: rates op WATElt AI^D heat’; loss PROM RESPIRATORY TRACT, 191 v,

and 67) . Tlie rooin conditions were then changed to make it warm, with , a mean :
temperature of 35.7° C.- (extremes, 35 and 36.6) and a- relative humidity of 56,
per cent (extremes, 50 , and 65) .. The temperature of the room was made ’

warmer: the mean temperature was ’38.4;° C. (extremes, 37.7 and 38.9) and
relative humidity ivas 49.2 per cent (extremes, 41 and 66). Higher room
temperatures could not be employed as they resulted in, marked discomfort with' - _
apprehension, increase in dyspnea, and, at times, even acute cardiac .asthma. ; ;

Measurements of the rates for water and heat loss were repeated for all four
atmospheric conditions in succession in most of the subjects. Measurements were
cheeked on another day, usually the next.

Comfortable environmatxt

Temperatute <sxr

E^Ls-tive Kumiclity of atr

(O

to

I

C«

«

to

v,.

IE23

Oi

I

a

N,

I

1

In

cv

to

V..

to

to

to

1

0)

)

to

Normal C H.P
dold ax^il (Z-nuironment

Fie. 1. — The temperature and relative humidity of the expired air of normal subiects and
patients with right and left ventricular con.gestive heart failure (Functional Class IV). The'
subjects rested, sitting quietly in a comfortable, and a cold and foggy^ room atmosphere. The
mean values are shown within the columns and the extremes are shown within the paren-
thesis above the colunms. '

RESULTS

The results are summarized in detail in Tables I, II, III, and IV, and Pigs.

1, 2, and 3. Pig. 2 should lie consulted for comparison with normal values re-
ported elsewhere.’ The statistical coihstants are shmm in the tables.

Temperature of the Expired Air . — ^Relative Humidity of the Expired Aii': '

The mean relative himiidity of the expired air when the room atmosphere was
cool and foggy was 82 per cent (extremes, 68 and' 91). The values changed to
84.5 per cent (extremes, 74 and 96) when the room was made comfortable. ^ ‘
Upon increasing the room temperature to 35.7° C. the relative humidity of the ^ .
expired air was 89 per cent (extremes,. 84 and 93).. When the room atmosphere
was made slightly drier and w^aimer the relative humidity of the air expired be- ’

came '85 per, cent (extremes, 77' and 91)., ConsuIt.Tables I through, lY for de- •

tails.. ' ' ■ ,

192

AMHinCAN' IfKAKT .TOimXAL

Jiaie of Walcv Ltm Frotn ihc Iitsjn'ralor}/ TrO( f.—Tho mean rah* oi' wak-r
loss was 0.991 Om. per .scpiore nieler of body area p<*r hat Tiiitint(-.s (extremes,
0.5839 and 1.3255) when the room envinnnnent was eool and foj^try. When the
room almos’idiero was enmrorlal)le, the mean rate was O.J>3J (extremes*. 0,497
and 1.482). U])on inereasiiifT the room temperature to make the enviroinnent
warm (35.7'’ 0.) llio mean rale, of loss was 0,952 (exircmes, O.CfiO and 1.208),
When the room atmosphere wa.s ?nnde .s'H»rhtly wanner and drier the rate heeame
0.798 (extremes, 0.456 and 0.973).

rv»»ol tvRTK}) CV»o) (v*i©) cv«>«<k fv«*oi

EaleofAiE- T2<ate EyipinatKan Temp'^ptred IS;! Humiciitxj Eats Water Pate Ksat loss Pj \,\bbrHeai£os5
Irpi^ation or COt Air C** ol E'>cpircdAit?6 loss EX«cor Water fhji

VrriVOmin t/mViOmirv ^ /mVOmm c«l/^Ti>/)Ofn,n

FJp. 2.1.

Figs. 2A anti 2/J. — Tlip rolution'-lilps of llie rates of liter anti lioat losses from tlie re-
.spiratory tract in patients niUi rlglit anti left ventricul.ar congestive heart failure (Functional
Class IV) under various cnvironiuenlnl condUlons. All patients rested sltllnK quietly. In order
to use a common ordinate, the true values (V) were recorded as multiples of ten. The actual
values are Indicated with the means within the columns and the ranBCS in parentliescs above
the columns. The flgure was broken Into part.s A and B for convenience. .\11 measurements
were made simultaneously for eacli subject at each condition of the room air.

Fate of Irrigation of the Respiratory Traci With Air . — ^Tlie mean rate of
irrigation of the respiratory tract wilii air was 46.860 litoiis per sfpiare meter
of body area per ten minutes (extremes, 31.431 and 64.043) when the environ-
ment was cool and foggj*. When the room eonditiolrs were made comfortable,
the mean rate became 44.833 (extremes, 25.381 and 70.259). Upon rai.sing the

BURCH : RATES OF WATER ■ AND ' HEAT LOSS IHIOM RESPIRATORY TRACT ^ 193

room temperature to 35.7° G., the mean rate was 51.991 (extremes, 41.993 and
60.052), In a slightly warmer and drier atmosphere, the mean value ivas 49.588
(extremes, 28.003 and 59.295)', , . ^

There was a high positive correlation between the rate of irrigation of the ;
respiratory tract ndth air and the rate of water loss (Fig. 3), This was true
for all four environmental conditions and is in keeping vutli similar findings
for comfortable environments in normal subjects and patients, with congestive
heai-t failure.^’ - From Fig. 3, it is noted that the correlation tends to be slightly
lower under conditions of the warm environment.

45

40

35

30

■25

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10 (0
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10' to
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w 1}. to
to 10
55 *0 52

Vi >1^ Vi

0 i

s

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VO

CM

r

R

a

o

0
+;

1 <0
£ 0

Vj +

0

n Comfortable envi.ron.ment
^ Cold and environment

B V/arm environment

VO

K

CO

n

N;

o/

A.

o

Nom^l cue:”' N ormal CHE

U

a

<o

'i-
•o

r., +

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5: S
^ S
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N. ^

5 §

S r
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I 1
in Q
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in t*

Nornwl C.H.F Normal C.W.F

(VX»00) CVX»00> CVXlO> IV X lO)

cvxloo) (vyioo>

(VXIO) (VXfO)

itortnal

cvmo)

C-H-H

tv X lo)

ifortml G.RF tformal O.H.P

Ra.te:h^lo5S ‘RafeODi.ttea.t
byliberabonctCOa tossChco’i

cal/tn*/IOmin. ot total

Rate heat bs5 "Rate heal bss
bgconvedionfrict bycDnwectioncha

cat /mV le min ®/o ot IoIaI

'Bate total lunto
tieaibssCHl

cal./mViomin.

'Rate total lurto
heatJossCH)
% ot total

'Rate total bod
heat loss
cal /mViOmln'

Pig. 2B. — (For legend see Fig. SA.)

Rates of Heat Loss From the Respiratory Tract . —

1. Eate of Heat Loss From the Vaporization of Water, Iie : When the room
environment was cool and foggj', the mean rate of heat loss, by vaporization of
water (Iie) was 0.553 calorie per square meter of body area per ten minutes
(extremes, 0.335 and 0.762). This reiiresented 6.54 per cent of the totaLbody
beat loss dr 49.8 per cent of the total heat loss from the respiratory tract. The
mean rate of heat loss from the vaporization of water was 0.539 calorie per
square meter of body area per ten minutes (extremes, 0.286 and 0.868) when

194

AMKIUOAK in^AKT .TOmtKAl*

the room atmosphere was eomforlablc. This represented about fn4H per cent
of the total loss of body heat nr 62.7 per cent of the total bent lost from the
rospiratoiy tract.

Wlien the room temperature was increa.sed and the room v.ois made warm
(35.7® 0.) the mean rale of bent loss (hj;) was t).-552 <-aloric per square meter
of body area per (on minutes (extremes, 0.380 and 0.708), Tliis represented
6.61 Iter cent of tlic total heal lost from the body or 61.3 per (‘Ciit of the total
lieat lost from the respiratory Irart. Upmj making the rwun sliphtly warmer
and drier the mean rale l)Ceame 0.161 f-alorie (exfrcme.s, 0.262 and 0.560). This
represented 5.39 per cent of the tofal h«'nt lo.ss or (52.3 per eent of the total heat
lost, from the rcsj)iraloTy tract.

I'"

214

>^ 1 ?-

I

|.o

■$ 8

'■i.

o

o

• Cotifortftble enrlronneat

* Cold aad foggy environa^nt
=t-‘ Worn onvirotnont

4 •

%

£5 30 3^) ^-0 -50 30 3r> 60 6^ TO

Rale ot irn^Uonct rcspinsloro iMctuiiltv air

Fifj. 3. — -V spot prj'pa to lUu^tratc tlio hlKh correlntton of tho mlo of IrrlB-'ilion of th!'
respirator.v tract -with air ami tho nite of water Io-or from the resi^Iratory tnicU The p.atlcntP
wltii rlfcht and left ventricular coneeatlvo heart failure < Functional Class IV) rested sUtinE
quietly. The correlation was RTcater at the cold and comforfablo environmental atmospherjc
condltion.s than at the warm one.s.

2. l?ate of Heat Loss From tho Deeomposition of Uavbonie Acid and the
Excretion of Carbon Dioxide, hco.s: The mean rate of heat lo&s from tho ex-
piration of carbon dioxide, hoo... was 0.301 calorie per square meter of body
area per ten minutes (extremes, 0.261 and 0.370) when the environment was
cool and foggry. This represented 3.61 per cent of the total body heat loss or
27.4 per cent of tlic total lo.ss from the rcspiratoiy tract. Wlien the room at-
, mosphere was made comfortable, tho mean rate of heat loss (hco^) was 0.293
_ calorie (extremes, 0.225 and 0.3S7). This represented 3.58 jier cent of the total
. loss of body heat or 31.9 per cent of total heat loss from the raspii-atorj’- tract.

When the room temi)erature was increased to pinduce a wann atmosphen:
(35.7° 0.), tlic mean rate wa.s 0.302 calorie (extreme.s. 0.247 and 0.387). Tliis
represented 3.63 per eent of the total heat lost from the body or 36.2 per cent

BimCH: KATKS OF WATER AND II KAT LOSS FROM IiK*SPIRATOEY TRACT

of the total heat lost from the respiratoiy tract. When the room emdromnent
was made slightly w-a.mier and drier, the mean rate of heat loss was 0.315 calorie
(extremes, 0,272 and 0,361). This represented 3.69 per cent of the total heat
lost from the body or 42.6 per cent of the total lo.st from the respiratory tract.

3. Rate of Heat Loss by Convection, Warming, Inspired Air, lie- ^Vlien
the room environment wa.s made cool and foggy the mean rale of heat loiss by
warming inspired air, he, Avas 0.254 calorie per square meter of surface area
per ten minutes (extremes, 0,150 and 0.361). Thi.s represented 2.99 per cent
of the total heat lost from tlie body or 22.0 per cent of the total lost from the ■
re.spiratory t,racl. When the room atmosphere Ava.s made comfortable, the mean
rate Avas 0.162 caloric (extreme.s, 0.091 and 0.248). This represented 1.95 ])er
cent of the total heat lost from the body or 17.6 per cent of the total heat lost,
from the respiratoiy tract.

Wlien the room atniosphere Avas made warm (35.7*^ C.) there was a slight .
mean gain in heat, bj' expiring cooler ah', of O.QOS calorie per square meter of
body area per ten minutes (extremes, -f).018 and -f 0.060), This represented
0.002 per cent of the total heat lo.st from the body or 0.2 per cent of the total
loss from the respiratoiy tract. When the room atmosphere wa.s made slightly
warmer and drier there Avas a mean gain of 0.036 calorie (e.xtremes, +0,019 and
•f0,051). This repre.sentod 0.004 per cent of the total heat lost from Ihc body
or 0.5 per coni of the total lost from the re.spiratory tract.

4. The Rate of Total Heat Loss From the Respiratoiy Tract, H: In tlic
cool and foggy envij-onment, the mean rate of total heat lo.ss from the re.sjiira-
toiy tract, H, Avas 1.111 calorie,s per square meter of body surface per ten min-
utes (extremes 0.760 and 1.166). This represented 13.2 per cent of the total heal
lost from the body. When the room conditions Avere made comfortable the mean
rate Avas 0.918 calorie (extreme.s, 0.631 and 1.503) or 11.2 per cent of the total
rate of heat lost from the body. Upon making the room atmosphere warm
(35,7° C.) the mean rate became 0.858 calorie (extremes, 0,645 and 1.010) or
10.3 per cent of the total body heat loss. Wlicn the room air was made slightly
Avarmer and drier the mean rate became 0.740 calorie (extremes, 0.515 and 0.835)
or 8.7 per cent of the total body heat loss.

5. The Rate of Total Loss of Body Heat: Tlie mean rate of total body
heat loss in the cool and foggy environment was 8.43 calories per square meter
of surface area per ten minutes (extremes 7.28 and 10.18). When the enAdron-
ment Ava.s comfoilable the rate was 8.20 ca]orie.s (extremes, 6.56. and 10,50).
Upon making the room air Avarm (35.7^ C.) the rate of total body, heat lo.ss
was 8.34 calories (extremes, 6.75 and 10.50). The value became 8.52 ealorie.s
(cxtreme.s, 7.51 and 9.53) in a .slightly Avarmer and drier atmosphere.

General' Ecactioiu.—AW patients. did not enjoy the comfortable eiiviron-

inenial conditions. iSEost of them found tlie cool and foggy atmo.sphere inieom-
fortably cool and avouIcI not like to remain under such conditions loo long. lu
some instances, the patients insisted on covering themselves with woolen blankets.
The patient.s did not o}).iect to the Avarm environments, and some of the Negro *
patients even preferred them. They all admitted that lim temperature Avn.s ton

•196

AJIERICAN HEART JOURNAL

Table I. The Rates of Water and Heat Losses Fiiojt the Respiratory Tract of Nine

CiAss lA'’). The Subjects Rested Sitting

SUBJECT

AGE

(yr.)

SEX

RACE

ENVIRONMENTAL

AIR

AUl

IRRIGATING

LUNGS

COj

EXHALED

EXPIRED

AIR •

D.B.t

“0.

L./M.2/10*

L,/M.2/10^

D.B.f
^ C.

R.II.t

.%

1

31

M

N

16.1

89

31.431

1.307

33.7

82

2

27

F

N

15.3

97

46.335

1.310

33.6

91

3

44

F

W

14.2

97

44,232

1.266

33,6

79

4

53

F

N

15.5

89

30.370

1.398

33.6

86

5

41

F

N

14.4

94

4G.277

1.502

33,9

88

6

49

M

W

13.3

94

64.043

1.764

33.6

68?

7

C6

F

N

12.2

100

56,752

1.751

34.1

83

8

35

M

N

10.5

90

42.474

1,256

32.5

78

9

56

M

N

13.3

100

59.853

1.484

32.7

79

Mean

13.9

94

46.860

1.448

33.5

82

Standard

1LG6S+

0.112±

0.4+

6.8+

deviation

2.750

0.026

0.09

0.16

Coefficient of

24.9±

7.73±

1.19±

8.24±

variation

5.87%

1.82%

0.28%

1.94%

Range

10.5

89

31.431

1.256

32.5

68

1(5.1

100

64.043

1.764

34.1

91

♦These units aie measured in sQuare meters per ten minutes.

tD.B. = Dry bulb.

tR.H. =: Relative humidity.

1

Table II. The Rates op Water and Heat Losses From the Respiratory Tract op Ten

Class IV). The Subjects Rested Sitting

1

ENVIRONMENTAL

AIR

AIR IRRIGAT-
ING LUNGS 1

CO.

EXHALED I

EXPIRED 1

AIR 1

IVATER

LOSS

AGE

GM./il.V

SUBJECT

(YR.)

SEX

RACE

D.B.t

K.II.t

L./M.V10*

L./M.VIO*

D.B.t

R.H.t

IT^

1

31

M

N

21.1

55

35.112

1.072

34.0

82

0.6575

2

27

F

N

20.0

67

48.909

1.437

34.1

96

1.2034

3

44

F

W

20.3

63

44.232

1.446

.33.7

79

0,8000

19.7

57

47.897

. 1.446

33.6

86

0.8773

4

53

F

N

20.5

57

25.381

1.075

33.6

83

0.5421

20.3

57

26.350

1.294

33.6

77

0.4972

5

41

F

N

21.1

64

44.333

1.502

33.9

88

0.9442

6

49

3M

W

19:7

59

53.972

1.579

33.9

74

0.9638

8

35

U

N

20.0

57

35.619

1.256

33.6

81

0.6801

10

67

M

•N

20.0

54

55.908

1.464

33.1

82

1.2063

11

52

M

N

20.3

56

44.204

1.442

33.6

91

1.0940

12

54

U

N

20.0

55

70.259

1.844

32.9

87

1.4817

Mean

-

20.3

58

44.883

1.398

33.5

84.5

0.9306

Range

19.7

54

25.381

1.072

32.5

74

0.4972 ,

21.1

67

70.259

1.844

34.1

96

1.4917

Standard

12.42±

0.19+

0.49±

6.5+

0.35±

deviation

2.44

0.04

0.10

1.3

0.07

Coefficient

27.6±

13.6±

1.46±

7.6+

37.6+

of variation

5.4%

2.7%

0.28%

1.5%

10.4%

♦These units are measured in square meters per ten minutes.
tD.B. = Dry bulb.

VR.H. = Relative humidity.

; ' BURCH : RATES OP WATER ANt) HEAT LO§S PROM RESPIRATORY TRACT 197

?ATiENTS 'With Bight and Left Ventricular Congestive Heart Failure (Functional
Quietly in a Cold and Foggy Boom Atmosphere

rate op heat loss

WATER VAPORIZED

liberation op COj

WARMING AIR

TOTAL LOSS FROM

1 LUNGS

TOTAL' ■
HEAT LOSS

gm./m;2/

CAL./M.2/ 1

% . 1

CAL./M.2/

%

CAL./M.2/ 1

% 1

CAL./M.2/

%

CAL./M.2/

10*

10* 1

TOTAL

10*

TOTAL

10*

TOTAL 1

10*

TOTAL

10*

0.5829

. 0.335

4.41

0.274

3.61

0.151

1.99

0.760

10.00,

7.59

1.0692

0:615

8.01

0.275

3.58

0.232

■ 3.02

1.122

14.61

7.68 ,

0.8910

0.512

6.81

0.266

3.54

0.235

3.13

1.013

13.47

7.52

0.6676

0,384

4.78

0.294

3.66

0.150

1.87

0.828

10.31

8.03

. 1.0504 ■

0.604

6.97

0.315

3.63

0.247

2.85

1.166

13.45

8.67

1.0397

0.598

"5.87

0.370

3.63

0.361

3.55

1.329

13.06

10.18

. 1.3245 •

0.762

7.52

0.368

3.63

0.340

3.36

1.470

14.51

10.13 ,

0.8837

0.508

6.98

0.264

3.63

0.255

3.50

1.027

14.11

■ 7.28

1.1437

0.658

7.49

0.312

3.55

0.317

3.61

1.287

14.66

8.78

0.9614

0.553

6.54

0.304

3.61

0.254

2.99

1.111

13.13

8.43

0.3413±

0.125±

1.241

0.040+

0.0411

0.0741

0.6731

0.2261

1.651

1.141

0.057

0.029

0.29

0.009

0.010

0.017

0.159

0.053

0.38

0.27 '

25.10±

22.5861

19.021

13.161

1.141

29.131

22.511

20.341

12.581

13.501

5.92%

5.324%

4.48%

1.31%

0.27%

6.18

5.31

4.79

2.97

3.18 '

■ 0.5829

0.335

4.41

0.264

3.54

0.150

1.87

0.760

10.00

7.28

1.3245

0.762

8.01

0.370

3.66

0.361

3.61

1.166

14.61

10.18

Patients With Bight and Left Ventricular Congestive Heart Failure (Functional
Quietly in a Comfortable Boom Atmosphere

RATE OP HEAT LOSS

'

WATER VAPORIZED !

LIBERATION OF COj

WARMING AIR

TOTAL LOSS PROM
LUNGS

TOTAL

body

HEAT LOSS

CAL./M.2/
10* .

% .
TOTAL

'CAL./M.2/

10*

%

TOTAL

CAL./M.2/

10*

%

TOTAL

CAL./M.2/

10*

%

TOTAL

CAL./M.2/

10*

. 0.378

5.40

0.225

3.21

0.124

1.77

0.727

10.39

7.00

0.692

8.41

0.302

3.67

0.188

2.28

1.182

14.36

8.23

0.460

5.41

0.304

3.58

0.162

1.91

0.926

10.89

8.50

0.5O4

6.09

0.304

3.67

0.182

2.20

0.990

11.96

8.28

0.312

4.76

0.228

3.48

0.091

1.39

0.631

9.62

6.56

0.286

3.84

0.272

3.65 .

0.096

1.29

0.654

8.78

7.45

0.543

6.18

0.315

3.59

0.155

1.77

1.013

11.54

8.78

0.554

5.89

0.332

3.53

0.201

2.23

1.096

11.66

9.40

0.391 .

5.37

0.264

3.63

0.132

1.81

0.787

10.81

7.28

0.707

8.29

0.307

3.60

0.200

2.34

1.214

14.23 .

8.53

. 0.641

7.60

0.303

3.59

0.161

1.91

1.105

13.11 '

8.43

0.868

8.27

0.387

3.69

0.248

2.36

1.503 . -

14.31

10.50

0.539

6.48

0.293

3.58 ,

0.162

1.95

0.918

12.00

8.20 .

0.286

3.84

0.225

3.21

0.091

1.29

0.631

8.78

6.56

0.868

8.73

0.387

3.69

0.248

2.36

1.503

•14.36

10.50

0.1741

1.60±

0.0421

0.121

0.0331

0.3441

0.21+

2.21

0.99+

0.034

0.31

0.008

0.02

0.006

0.067

0.04

0.4

0.19

32.31

24.71

14.31

3.01

20.31

21.231

22.81

18.51

11.9±

.6.3%

4.9%

2.8%

0.6%

3.9%

4.1%

4.5%

, 3.6%

2.3%

198

AMEKICA-V XIEAUT JOURNAL

TabiiD m. 'J'he Kates of ^Vateu anj) Heat Tajrses From tjie KESi'iitAToitv Tract ok Eight

Class IV). Tjie Patients Rested Sitting

-

ENVIRONJIENTAI,

.VIU

AIK IRKIGAT-
ING LUNGS

CO;

EXIT AI, ED

AIR

expired

AVATER

LOSS

AGE

1 SEX

D.n.t

R.ir.}

D.B.f

1 R.n.t

QM./M.2/

SUBJECT

(YU.)

RVCEi

°C.

L./M.V10^

L./.\r.2/J0*

"C.

1 %

'10*

t

31

K

35.0

41,993

1.170

30.0

84

0.6604

' 2

27

F

N

35..5

54

54.977

1.310

;:o.4

93

0.9432

> 6

49

tv

36.0

01

00.0.52

L671

34.0

88

0.8788

7

CO

F

N

30.1

.50

.58.000

1.400

30.9

89

1.1770

8

3o

:m

N

35.0

.50

43.368

1.242

35.4

87

0.9075

10

G7

]\r

N

, .35.0

oil

.59.601

1.488

35.0

90 ■

1.2081

n

.52

i\r

N

35.0

42.474

1.383

.30.1

88

0.8113

12

.54

yf

K

36.4

.50

.55.400

1.844

35.3

89

1.0289

Mean

35.7

50

.51.991

1.4.39

35.8

89

0.9520

Range

.35.0

50

11,993

1.170

34.0

84

0.6604

3(i.O

05

00.052

1..844

30.9

93

1.2081

.Standai (1

7.999±

0.219±

0,8.3±

2.0±

n.269±

deviation

2.000

0.005

0.207

0.00

0.087

Coefficient

]5..3D±

15.22+

2.31±

2.94+

28.20±

of variation

3.85%

.3.81%

0.58%

0. 73 7o

i'.07%

*Those units me nietisurorl in square meters per ten minutes.
tri.E. = Diy bulb.

$R.H. = Relative humUllty.

Table H'". The Kates of Wvter and Heat Losses Pro.m the KEsMuA-roiiy Tract of Five

Class IV). The Patients Rested Sitting Quietly

ENVIRON.MEN'IWL
AIR 1

AIR

IKRIGATIXO

LUNGS

CO;

E.VHiVLED

j AIR

j EXPIRED 1

1

AVATER

loss"

SUBJECT

AGE

(yr.)

SEX

RACFi

D.B.f
" C.

R.n.}

%

[ L/M.2/10*'

L/M.2/10*

D.B.t
•> C.

R.ll.t

%

gm./m.z/

10*

3

44

F

W

37.7

52

59.295

1.350

30.1

8t!

0.9733

4

53

F

A

.38.0

52

28.003

1.2.04

.30.1

84

0,4500

5

41

F

X

38.0

oiy

57.937

1.719

30.1

91

0.8931

9

50

M

X

3S..3

41

54.598

1.484

35.5

* 1 /

0.8230

13

35

M

X

38.9

45

48.107

1.030

35.0

88

0.S445

Mean

38.4

49.2

49.588

1.498

35.8

85

0.7980

Range

t"»7.7

41

28.003

1.294

.35.0

77

0.4560

38.9

5G

59.295

1.719

36.1

91

0.9733

•These units are measured in .square meters per ten minutes.
tD.B. = Dry bulb.

JR.H. = Relative humidity.

high for continuous eonifort. Tliey eousidered tlie 20.3'^ (J. temperature of the
comfortable atmosphere top low for continuous use. Definite chilling tvould have
developed in several houi's. A temperature of about 2^^° or 25° C. tvould have
been more comfortable for continuous use when the relative humidity remained
about^50 per cent. Two of the patients were placed in a room tvith a temperature
of 115° C. and 49 per cent relative Jiumiditj'. This resulted in extreme dis-
comfort with dyspnea, restlessness, and irritability. They were not able to
vdthstand the high temjjerature long enough for obsei-vations of heat and water
loss. Because of this experience v'ith Iavo of the sub.ieets, others Avei-e, not
sub.ieeted to such hot atmosphere.

BUBCEi: RATES OF WATER ' AND HEAT LOSS FROM' RESPIRATORY TRACT 191

Patients With Bight and. Left Ventricul^ik Congestive Heart Faliure (Functionae
Quietly IN A Warm Atmosphere , ' ' ■

RATE OP HEAT LOSS

j

. ' WATER VAPORIZED • ■

1 LIBERATION OF CO.

AV ARMING AIR

' TOTAL loss' FROM ' I
LUNGS ' • 1

1 TOTAL

BODY

'heat LOSE

- %

'■■ % .j

GAL./M.V

CAL./M.V

•%.

1 CAL./M.2/

TOTAL

TOTAL

10'^

TOTAL •

10-* 1

TOTAL

10*

: 0.380

5.63

0,247.

3,66

0.018

0.27

0.645

9.56 '

6.75

: 0.542 .

7.06

, 0.275

3.58 -

0.014

0.18

0.831

10.82 •

. 7;68.

0.505 '

5.19

0.351

3.61

^0.033

+0.34

0.856 '

8.78 '■

9.73

0.677

7.55

0.294

. 3.28

0.013

0.14

0.984

10.97

8,97

. .0.522 ,

7.27

0.261

.3.64

0.005

0.06

0.788

3.0,97

7.18

0.708 •

- 8.21

0.312

3.62

+0.010

+0.12

1.030

11.72

8.62 -

, 0.475

6.49

. 0.290

3.96

+0.060

+0.08

0.771

10,53

7.32

" . 0.603

5.74

. 0.387

, 3.69

0.014

+0.13

0.976

9.30

30.50

; 0.552

6.64

0.302

3.63

+0.008

+0.002

. 0.858

10.33

8.34

0.380 .

5.19

0.247

.‘1.28

-0.018

-0.27

0.645

-8.78

6.75, .

0.708

8.21

0.387

3.96

+0.060

+0.34

3.010

11.72

30.50'.

. O.lOot

■ .0.980±

(l.042±

0.720±

0.033±

0.200±

0.115±

0.977±

1.258+

. 0.026

0.245

0.013 '

0.180

O.OOS

0.050

0.029

0.244

0,315

; 19.02+

.14.76±

J.3.901

J9.83±

412.50±

100±

33.40±

4.58± ’

15.08+

4.76% .

3.69%

00

4.96%

103.13%

25%

3 : 35 %

1.15% ■

3.77%

Patients With Bight and Lefi' Yentricolar Congestive Heart Failure (Functional
IN A Fairly W.(Vrm Boom" Atmosphere

RATE of heat LOSS

WATER VAPORIZED

WARMING jUK

TOTAL LOSS FROM
LUNGS

total

HEAT
LOSS '

C.VL.'/.M.2/

%

C.VL./M.2/

• % .

CAL,/M.2/

%

. 10*

TOTAL

30* ■

TOTiVr,

10 *

TOTAJj

,0.560

■ 7.14 ■

0.285

3,64

+0.026

0.819

30.45

0.262

3.49

0.272

3.62

+0.019

+0.25

0.515 ,

(i.86

7.51

0;514

5.39

0.363

3.79

+0.040

+0.41

0,835

8.76

9.53

■ 0.473

5.39

0.312

3.55

+0,042

+0.48

' 0.743

8.4()

8.78 •

.0.495

5.52 ' ’

0.344

.3.84

+0.051

+0.60

0.788 •

8.79

8 .f)(j

0.461

5„39

■ 0.315

3.69,

+0.036

+0.41

0.740

8.l9i .

' 8.52 .

,0.262

3.49 .

0,272

3.55

+0.019

+0.0025

0.535

6.80

7.51

. 0.560

. 7.14

. 0.363

3.84

+03)53

+0.0060

0.835

1 0.45

9.5.3 ■

DISCUSSION

Eig.' , 2 illustrates graphically tlie relationships of the rates of- .wal er aiK
lieat loss from the respiratom^ tract in normal subjects and patients suiferinj
wdth congestive heart failure. The enviromnental conditions were cool, am
foggy, comfortable, and warm. It is noted that the rates of both water and hea
loss tended, to he i^lightly higher in, the patients with heart failure. Detailei
comparisons could notjie made ndth the normal subjects for the warm at
mosphere since .the latter were studied mainly at higher atmospheric tempera
^ tures. , The relationships were essentially the same, liowever, as for the lower tern
peratures in the few instances where comparisons were possilile. These findimr

200

AMERICAN HEART JOURNAL

are in keeping with results found for other normal subjects and patients with
heart failure resting in a eomfortable environment.^

It is also evident from Fig. 2 that a wann environment stimulates the rate
of irrigation of the respiratory tract with air. This stimulation is not the result
'of an increased demand for oxygen to meet metabolic requirements, for the rate
of oxygen consumption did not rise under warm eiiA-ironmental conditions.
The precise mechanism by which warm environmental air stimulates respiration
is unlmo^vn. It is possible that there is a psychic element since a hot atmosphere
(115° to 120° F.) resulted in marked apprehension and a sense of suffocation.

It was noted in a preAuous reporF that the presence of free fluid in the lungs
due to the heart failure did not increase the rate of water loss from the lungs.
The greater rate of water loss encountered in the patients with heart failure was
due to the dyspnea and more rapid irrigation of the respiratory tract with air.
Reasons for the failure of greater water loss in the presence of free fluid in
the lungs were discussed in the previous rejiort.’

Although the cool foggy atmosphere was uncomfortable, it did not result
in any differences in the rates of water and heat loss from that observed in a
comfortable environment. Tlie warm environment did result in a slight change
in the rates, especially the rate of ventilation of the lungs. This increase over
the normal indicated a detrimental influence on the respiratory tract in the
presence of congestive heart failure. When the room air was made hot and
humid (120° F. and 49 per cent relative humidity) the patients were not able
to remain in the hot atmosphere long enough to complete an observation, because
of mai’ked dyspnea and even acute cardiac asthma. The normal subjects were
able to remain under such hot and humid en\ironmental conditions for prolonged
periods of study without showing respiratory and circulatory embarrassment.

These studies, as well as those previously reported,^ indicate the need for
ensuring a comfortable environment for patients with congestive heart failure.
Although a cool and foggy environment does not exert so great a stimulatoiy
influence on the respiratoiy tract as a warm or hot and moist environment, pa-
tients who must lead a quite existence cannot rest when they are uncomfortably
cool. This indicates the need for greater use of air conditioning of hospital
wards and rooms of cardiac patients. Likewise, this suggests the value of living
in a eomfortable balmy climate instead of a cold or hot one while under treatment
for congestive heart failure. Patients with anginal failure were not included in
these studies.

SUMMARY

Patients Avith congestive heart failure, Functional Class IV, moderately
severe, were studied to learn the influence of variations in the environmental
temperature and humidity upon the rates of Avater and heat loss from the respira-
tory tract. It was found that these rates were essentially the same for cool
and foggy, and comfortable emdronments. The patients AAuth congestive heart
failure did not differ significantly from the normal under those atmospheric con-
ditions. In a Avarm enAuronment, the rate of irrigation of the respiratoiy tract

BURCH: RATES OF WATER AND HEAT LOSS FROM RESPIRATORY TRACT 201

with air was definitely increased ; an increase out of proportion of the demands
for oxygen. There was also a tendencj’- for a slight increase in, the rate of water
and heat loss from the respirator^'' tract.

The patients were unable to stand the veiy hot and humid atmospheres.
Two reacted rather dramatically with dyspnea, apprehension, and even acute
cardiac asthma. Because of these reactions, observations could not be satisfac-
torily conducted.

These studies indicate a greater need for ensuring a comfortable and balmy
en'vironment or climate. These patients must be kept quiet physically and there-
fore are lilvely to be uncomfortable in a cool climate. A very hot climate or at-
mosphere is detrimental. There is a need for greater use of air conditioning
to ensure atmospheric comfort, especially in hospital rooms and wards where
cardiac patients are under treatment.

The author wishes to express an extreme appreciation to Mr. G. Morga^'i for Iiis keen
interest and important technical assistance in these studies.

REFERENCES

1. Burch, G. E.: The Bates of Water and Heat Loss From the Respiratory Tract of Pa-

tients with Congestive Heart Failure Who Were From a Subtropical Climate and
Resting in a Comfortable Atmosphere, Aji. Heart J. 32: 88, 1946.

2. Burch, G. E.: The Influence of Environmental Temperature and Relative Humidity on

the Rate of Water Loss Through the Skin in Congestive Heart Failure in a Sub-
tropical Climate, Am. J, M. Sc. (In press.)

3. Burch, G. E.': A Study of Water and Heat Loss From the Respiratory Tract of Man.

Methods: I. A Gravimetric Method for the Measurement of the Rate of Water
Loss, II. A Quantitative Method for the Measurement of the Rate of Heat Loss,
Arch. Int. Med. (In press.)

4. Nomenclature and Criteria for Diagnosis of Diseases of the Heart by the New York

Heart Association, New York, 1942,

TirK MFKEUT OF M1'L\LS (JN TIIK JiLFOTROOAHDJCXHLAM L\

xVoinrAL suo.iiv(j'r}j

Frnst Si]monson% M.D.. Howaiu) Ai,RXAKm;i!, Pn.l).,

Austin' rEuNSCHKi,, rii.!)., ano Axri:i, Ki:vs, Pii.D.
JTiXN'r.vroi.is, Minx.

A ny method a.s widely used in clinical medicine and applied physioloj^y as the
clcclToenrdioprnrn should he carefully standardized. This means that all
conditions and factors which miuiit aFeci the clcftroeardioiiram should ho reco'r-
nizod and considered. Tn view of the known itdluenco of meals on most circula-
tory functions, it i.s surprisinjf that no exi>erimenta1 .study on the influence of
meals on the elcctrocardioirram has been reported except a preliminary coin-
nuinication by Gardberj^ and ()lseti.‘ They investigated niiic normal youne
adults before and thirty minutes after an “ordinary mixed meal.” Apparently
only one ex])ei‘iment was made on en<‘h subject. Seveji showed a decrea.se of the
T wave in Lead I or TIT, or in all three standard lead.s. There wa.s no correlation
Avith the heai-t rate and no sullieienl axis chiiime to explain the change of the
T wave. Tn “.several othei- .subjects’* it was found that tlte T-wavo chnngc.s per-
sisted for two or two and one-half hours.

The authors regarded their material a.s insuflicient to arrive at final eou-
clusions. In this T^ahoratory. several elect rocardiogi-aphic siudies arc in i>ro"res.s
concerning the effect of various nutritional stales and ])hysiologlc stresses. For
this reason, avc were interested in the standardization of the conditions under
Avhicli the elect roeardiogi-am is taken. 'NYo thought that a special study of the
iutluenec of meals on the elect roenrdiojiram wo\ild he neee.ssary for the research
program hei’e and inigiit have valuable cliuieal applienlious. since many cardiac
patients complain of distress aftei' meals.

In order to arrive at an exact i>rodiction of normal limits of electrocardio-
graphic changes after food intake, the rc.sulls were treated mathematically using
the nsnal /-test as well a.s a now j)rocedure ba.sed on the nnaly.sis of variance.^

MJCTHOU

The basic .scries consists of 72 experiments on 12 normal subjects'*^ Avith the
three standard leads taken immediately before and thirty minutes after tlic meal.
Tlie electrocardiograms before the meal Avore taken four to fiA’c hours after a

, From tho Laboratory ot Physloloslcal Hygiene. University of Minnesota, AUnneapoUs,
Minn.

The work de.scribed In tills paper was done, in part, under a contract recommended
by the Committee on Medical Research, between the Olhce of Sclentinc Research and Develop-
ment and the Regents of the University of Allnnesota. Important nssls^ncc was provided by
the Sugar Research Foundation, Inc., and the Notional D.airy Council, Chicago, acting on be-
half of the American Dairy Association.

Received for publication Dec. 17. 194ii.

•All subjects were volunteer.^ assigned to tills Ijsiboratory for Civilian I’ublie Service bj
the Selective Service System.

202

SIMONSON ET AL; : EFFECT OF MEAIjS ON EEEGTROCAUblOGRAjM ' ,20o

light breakfast. .The subjects Avere young ilion from 19 to 32 years of jage. '
During the jierioci of the experiments and for about six months' prior to this
series, they were living in this Laboratory under controlled conditions of aetmty,
rest, and nutrition. During this period they were frequently examined with-
clinical and physiologic methods ; no evidence of disease Avas found in anj’’ of .
our subjects. This Avas true also for one of our subjects AAUth a borderline left
axis deAuation.

The test meals varied in composition in tlie iolloAving Avay ; Aveight, 200 to ^

' 26& grams ; total calories, 942 to 1 .548 ; carbohydrate calories, 41 to 61 per cent :
protein calories, 9.2 to 14.2 per cent ; fat calories, 29 to 43 per cent. In another
series (II) of 24 experiments on the same 12 subjects, the fat calories of the
meals AA^ere increased to 82.6 per cent, ^vith a corresponding decrease of carbo-
hj'drates to 14.3 and protein to 3.1 per cent, AA’ith a total caloric content of
1,437 calories. In a final scries (III) of 24 experiments on 8 subjects, three chest
leads (CFi, CPo, and CP 4 ) AA’ere taken in addition to the standard leads; further-
' more, the electrocai'diograms Avere taken thirty as AA^ell as sixty minutes after the
meal. In this series, the same mixed meals AA’^ere giA'cn as in -Series I.’^' The
place Avhere the chest leads Avere taken liefore the meal AA-as marked AA-ith a colored
. pencil in order to provide aeeiii'atc reproducibility in llie subsequent tracings.

Ill all three series, the lieart sounds AA'ere recorded simultaneously Avith the
electrocardiogram during arrested respiration. The folloAving intervals Avere
measured: duration of P Avave, duration of tlie P-E interval, QRS inteiwal, Q-T
interval, and duration of the meelianical systole, defined as the interval betAveen
the start of the major oscillations of the first heart sound and the beginning of
the second heart sound. Both Q-T interA’al (electrical systole) and mechanical
systole AA'^ere aA-eraged from five beats, usually in Lead II. The constant K Avas
calculated both for Q-T (Kqt) and mechanical systole duration (Kgyst), using
O-T 01 * svst

the formula K = — — — - Tlie average heart rate Avas calculated from ten

beats; in addition, the shortest and longest R-R intervals of the AAdiole record
Avere measured. Their difference Avas used as a criterion of. arrhythmia. The'
amplitudes of the P AA^ave, the QRS complex, and the T wave AA^ere measured
in all leads. The QRS axis and the T axis AA-^ere calculated, using Dieuaide’s ;
procedure. Since there Avas no significant change of the QRS axis, the usual '

. clinicar method for estimation of the over-all magnitude of the. QRS complex -
‘ as the sum of the amplitudes in Leads I, II, and III appeared to be suffieient
instead of calculation of the hypothetical manifest potential. In Tables I,. II,
III, and ly the symbol Sqrs will be used to ex])ress this A-aliie, A 'similar
. procedure Avas used for the T AvaA’Cs (At).

■ 'Statistical Methods. — ^Por the purpose of testing the statistical significance
of the effect of a meal, the t-test (Pisher,® Goulden'*) Avas used in all three
, series. Pof, the data of Series I, cohsisting of six trials on eachhf 12 subjects,
a more detailed analysis Avas possible. The a- allies' of the difference, d =' value

*The meals Jn all three series were always ordinary warm lunches, but .none of the food
. items was hot nor were strong spices or seasonings employed. Two glasses of liauids were
supplied, with each meal, a glass of cold water (from the tap) and a glass of cold milk (from
. an ordinary kitchen refrigerator). Neither coffee nor tea was provided;

20i

AMEUICAN UEAUT .TOUllXAIi

after meal minm value before vieul, were lubv^Uilcd in two-way tallies (trials
versus individuals), and tlio usual methods of analysis of variance (Fisher,
Goulden) were applied in order to break down llic total variation into its com-
ponents as shown in the following:

SOURCE OF VARIATION WEAN SQUARE DlXiRUm OF riiU-EnOM

Effect of the meal

v„

1

Individuals

V,

11

Trials

Vt

5

Interaction of residual

Vu

55

72

The term Vm is not usually included in such a breakdown, since it is merely
equivalent to 72 where d is the mean value of d. If we combine the last three
items (Vi, Vt, and Vu) we obtain the “total” mean square, Vt with 71 decrees
of freedom (df). The /-test referred to earlier is equivalent to the F-test:
F = which is simply the square of the value of /, But these equivalent

tests are not valid unless it has been shown that only a single source of variation
is present, that is, when neither P «= Tj/Vjt nor F >= is significant. As

this is virtually never the case with such data as thase at hand, a more suitable
test must be used.

The validity of the test which was developed rests upon a basic assumption.
We assume that the difi'crence d for individual b on trial b (which may he desig-
nated dull) can be expressed as the .sum of four comiionents duo, respectively, to
the effect of a meal, to the variation between individuals, to trials, and to inter-
action: duu = it + I), 4- Tk Rhk; and that each of the terms on the right is
normally distributed, Avith population variances anC', o-f", n't"*, and mt"*- If we
denote by ^r, -V, and .Vir unbiased estimales-’ derived from the sample of the
corresponding population variances, then wo have the equations:

Vn. = 72s„,= 4- 6s, ^ + 12 sr .S,t‘

V, — Gs,' 4- Sjt*

Vt = 12 Sr I .s,r

Vu =

These equations may be solved for sr, sr, and .su*.

Wilson® has suggested two tests, designated F' and F", to i*eplace the F-test
in the present situation. P*" and P" arc defined by :

F' =V',„/V,,
F" = V”„/Vt,

ra ~ Vt + V,t = 72 Sia~ + 6 S,* ;

V“„, = Vn. - V, -F V,t « 72 + 12 .-ir + 5,t=.

These are the tests that have been used on 'the present data. F' is a test of
whether the total variability is atlributablo to the joint action of individual and
residual variability, and P'' is a test of Avhetber the total variability is attributa-
ble to the joint action of trial and residual variability. These tests Avill be
further discussed by Alexander in a separate communication.®

SIMONSON ET AL. : EFFECT OF MEALS ON ELECTROCARDIOGRAM

o

. S

d

KS

'S

o

ci

o

o

cs

H

O

W

S

w

>

w

02

d

m

«

o

H

d

w

d

&

Hi

P

W

w

»

w

r^i

W

02

'

p

'

0

o

Ci

p

o

p

o

O CO CO r-i

t~>P -rtf

O to rii CO CO Cl

C2 O CO

+

o o t-

CO o

O t>» CO o o p o

O Cl T-i

O O p Ip

r-H d

ci fri oi o o <0 o

r-i d d

r-i rH

Cl

T— i

o

►-<

U4

TO

M

CO CO O lO

CO Ol o

O -if cq CO T-1 -dl

r-i CO rH

c

w

1

p p L- CO

O r“ CO

CO p Cl p P

O Tji O

W

o

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rH O OO

lo d lo d d d d

d d d-

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&

Ps?

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«

c

w

w

IP O t- to CO CO t>-

h!

5s,

t- CO CO

t-^ CO o

CO O i^i

o o o

O rti t-

lO O CO O O O

CO rH o

O O Ci rH

r-! d d

d r-j d d d d d

odd

TO

T-i

T-i

rH

c

-rj

01 lO 00

CO O Cl

Ip Ci CO cq CO <P

IP rti rd

I

O O Ci lO

b~ eo CO

<M rti t- O 1-i d lO

to CO lO

O O rH

o o o

Cl 1.0 Tji o o o o

o d o

CO

<

SO

CO CO CO

o o

lO O rji CO to r-i O

o to b-

o

O O Cl CO

03 rH CO

-1* t- o O r-l ca rjl

O CO CO

b

o

' ‘

O O rH UO

rH d CO

Cl -ii xji o o o d

rH O O

Ui

r-i r-f

CO

r-H

W

o:

&,

r-'f

^ CO O r-i

O gi

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r}l 1- iH

'»-,

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1^- cq c q

p

IP

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Ct:

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>-2

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<

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c*

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<

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d d •f d

r-< 1^5

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P P P o o o o

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d d d

rf

>

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03

ii'i

w

cc

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t-- t- CO

to •+ 00 rd 1-- fO CO

O 1- "dl

a

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r-i O -1<

r-t O to O O r-i Cl

0 0 03

d d O O

d d d

P P P o CO o o

o o o

p

w

+ + +

+ + 1

+ 1 I d- 1 1 1

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to r-t r-i CO Cl Cl lo

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tu

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d d d

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(jq P IP

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CO rji CO d d d d

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02

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1

5?

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no

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fp rp m

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20(i

.\MrcRfOAN IlKAKT JOnRNAfj

KESUI^TP

The various functions of the electroeardiof^miii did not respond in the
same way to a meal. Prom the slandpoini of slnli.stical evalufUion, the functions
may be subdivided into four groups.

Group A . — This group consists of eomijaralively stable funelion.s which
show only minor changes, hardly exceeding the tcclinical error of moa.surcmenl.
Those functions are: diu*alion of P, P*l? intonal, QlhS inlci-val, Q wave and
S-T segment. No tables are given for thc.so functions.

Group B . — Tilts group corisi.sts of function.s with fairly frequent but not
statistically significant changes. Tliis group incliulo.s p amplitude in Lead tl,
QRS^axis, range of heart rate, and The mean values are given in Table L

and the values of i, F' and P" arc given in Tabic II. Neither the f-lcsl, nor
the P' and P" tests are significant for those funelions.

Tabi.e it. STA-nsTio-vii Siflxrric.VKCK OF-EincrRoCARpiooRArmo Cn.AN«K.s Amu: rim Mr..^.i.

TEST (

r =V„/Vt

1 F' = v„,'/v,

! V" V..,VV,

j CROUP

Significance :
for 5% le\el

1.S4

o.m

for 1% loTcl

7.00

0.0,1

J0.20

. : finiction.'f;

O.H

1.1.'!!)

1.000

H (not .^ignili

^sysfc

0,.>7

u.fiOfi

0,737

vant)

P wave. Load IT

o.t.*; t

0.2.50

QRS axis

n.ooc

0.1 4C

4,024

*

B, Lead II

S).S)4

7.09vS

2.505

C (Mgnifieaht
with F test)

S QRS

10.70

7.700

l.OPl

T axi.s

14.00

3.810

r»Loos

Average heart rate

51.120

115.570

O ( significant

Systole duration

S8.7.';

43.240

1.50.130

with nil tests 1

QT interval

n7..'j0

20.37)7

70.08 1

Kqx

'cn.osi

15.307

17.412

T, Leah I

os.sn

44.75

.50.003

T, Lead n

lOO.Ot

73.70S

72.1 7S

18LC5

r>T.9 (0

00.2SII

log S T

IGI.7‘1

120.30

35,03

Group G . — This gro\ip consists of functions with con.si.stcnt changes, sig-
nificant according to the /-test but not according to the more refined P' and
P" tests. In this group we find the T axis, and the QRS and R-wave amplitude
in Lead IT. The mean values of these functions are given in Table I. and the
tests of significance are given in Table II.

Gro^ip D . — This group consists of functions whoso changes are highly sig-
nificant according to the /-test and also according to the P' and F" test.s. In
this group are average heaii rate, absolute value of'Q-T interval, K calculated
for Q-T, absolute mechanical systole duration, T amplitude in Leads 1 and II,
and 3 t. Although not listed in the tables, the significance of the change in the
T wave in Lead III is implied by the high significance of the T-wave changes in
Leads I and IT, and jifeau values for those functions are listed in Table I
and the tests of significance are given in Table II.

In Table I there are also shown, for the functions of Glroup D, the total
variability, the least significant differences due to the effect of a meal at the

SIAIONSOK’- KT AL. : EFI<’KC’J' OF AOiM^S ON ELEOTKOCAKWO^RAM 207 ^

,5 per cent and 1 per cent levels, and the range of least significant differences.
The total variability is defined b 3 ' 0 -^- = o-r -i- o-i~ -i- crit", where o-i, o-t, arid :
fTit are the population variances. ’ (r/ is thus the total variance of the dif- —
ference cl, the combined effect of the several sources, of variation. The least,
significant differences (LSD) are defined by LSD = ‘ 0-5 x t, where t is the ' .
5 per cent or the 1 per cent value of i with 71 df. Finally, the least sig-.
nificant -range is defined by (Mean - LSD) to (Mean -f- LSD). At the 5 per .
cent level, this 'gives the range within which 90 per cent of the obtained;
values of d nia^' bo expected to lie; similarly, 98 per cent of the obtained value.s
of d- may be expected to lie within the 1 per cent least significant range. Values
exceeding these ranges mjjy be judged almonnal, in comparisoji with our group 7
or normal young men.

Heart Rate. — The average heart rate increased by 7.1 beats per minute
after the meal, with a lotal variability of ±4.G7 (Table T). This increase was
highly significant (Table 11). Oji the other hand, there was no significant in-
crease of the range of the heart rate, calculated from the difference between
the shorte,st and longest R-K interval (Table I).' Therefore, there is no in-
creased tendency to sinus ainhythmia associated with the increased heart rate.

It will be noted that the heart rjite before the meal indicates sinus bradycardia
in the majority of our subjects. According to the experience of this Laboratory,
sinus bradycardia is i-athcr connnon among noinial young men.

Bnrnlion of Mechanical Systole, Q~T Interval, and Kqt - — With the

.shorteniiig of the R-E interval after the meal, a shortening of both the duration
of •the mechanical (syst) and of the electrical sy.stole (Q-T) should be expected!
Tins is indeed the case, as can be .seen in Table 1. The values are given in. ,
hundredths of a .second. The difference is small, but .statistically highly sig- ,
nificaiit (Table IT). The con.stant K would expi-ess whether the shortening
of mechanical (.syst) and electrical (Q-T) .sy.stole would, conform to the shorten-
ing of the,R-R intei-val i 7 i a proportion as indicated by the formula, or whether !
the change of Q-T or mechanical systole (.syst) is out of the normal proportion.
In. the fir.st ca.se, K would remain the .same; in the .second ea.se, K would change.
Tablets I and II .show that there is a highly significant increase of Kqt- This
means that the Q-T interval, although significantly shorter after the meal, does
7 JOt shorten quite in proportion to the decrease of^thc R-R interval. After’ .
, the meal, the Q-T interval is relatively larger than it was before the meal. In
contra.st, there is no .statistically significant change of KsystFin fact^ the dift'er- !
ence of the meairs is zero (Table I). However, this does not mean that KsjA
belongs to the Group A of .stable functions, TVsyst remained the )same withiji
± 0.002 in only 10 of 72 experiments; the changes exceeded ± O.OI in-
experiments. Occasionally, rather large changes were observed up to -f0,0.32 ^
and -0.024. The changes occurred in both directions and were erratic both . hr ,
regard, to individual and trial variabilitAr The different response of Egyst and
T^qt is not surprising. Discrepancies in the respon.se of Ksyst and Eq.t have •

: ; .beep , repeat edly observed under various experimental conditions. ® ’ !■ . ;

■ ' \ , :BnraU^^^ P Ifa.re.— The duration of the P .Avave. is e.ssentially the sanic "

JjefoJ'e and after the meal. : ' . " ,

/; A--

•»**«T*'

208

AMEKICAN HEART JOURNAL

P-B Interval. — There were no changes of the interval in 33 of 72
experiments. In one suijject, tiie P-R interval was consistently shortened (by
0.02 second) after the meal, while in the other subjects the changes were minor
or not uniform.

QR8 Inter val.—Tlhe. QRS interval was the same (within ±0.01 second)
before and after the meal. The QRS interval appears to be the most stable
of all electrocardiographic functions.

PAVave Amplihidc. — There were no changes in the amplitude of the P-
waves in Lead I. In Lead II, changes averaging between 0.02 and 0.03 mv,
in both directions (increase or decrease) were observed in 49 of 72 experiments.
An increase of the P wave (in one experiment by 0.1 mv.) ^vas more common
than a decrease, especially when the P Avave Avas small before the meal. The
changes AV'ere not statistically significant (Table II). In Lead III, the changes
of the P wave Avere similar to those in Lead II. If the P Avavc Avas negativ'e
or diphasic before the meal, there Avas a tendencj' toAvard gi'cater positivity after
the meals.

Q ^Yave. — ^In electrocardiograms Avithout a Q wnxe before the meal, no Q
Avave appeared after the meal. In electrocardiograms Avitli a .small Q Avave be- .
fore the meal, there Avas a tendency to a slight increa.se (not exceeding 0.05 niA'.)
of the Q Avave in all leads. Even so, the Q Avave remained small and insig-
nificant. Thus, the Q Avave may be regarded as a comparatively stable func-
tion (Group A).

BAVave AviplUndc in Lead 11 and — The R Avave in Lead II Avas
increased in 52 and decreased in 15 experiments. In several experiments, the
changes, especially increases, aa'cvc quite considerable (betAveen 0.3 and 0.5 mv.).
Due to a larger degree of variability, the aA'crage increase Avas slight (Table I)
and significant only for the F-test (Table II).

The distribution of changes of 2 qrs was similar to those of R, (55 in-
creases, 15 decreases). The average increase of 0.17 mv. aa-os highly significant
for the P-test, and aa'js also significant for the F' test (individual variability),
but AA^as not significant for the F" test (trial variability) (Table II).

No calculations of statistical significance Avere made for the S AA’ave, since
"changes of the S AAmA^e AAmuld be reflected in both Sqrs and QRS-axis changes.

QBS Axis. — The QRS axis remained unchanged (betAA'een ±2°) in 33 of
72 experiments. In the other 39 experiments there Avas about an equal incidence
of a greater right or left axis shift after the meal. Consequently, the average
electrical axis AA^as about the same before and after the meal (Table I). In
one subject Avith left axis dcAiation before the meal, there AA'as a consistent shift
tOAvard the right, so that the left axis deviation aa’os less pronoimced. Only
minor changes Avere observed in three subjects Avith an axis betAveen 75° and
89°, but the same Avas true also for another subject AAoth an initial axis betAA'een
15° and 21°. No consistent relationship betAA'cen axis change and initial axis
Avas seen in this series.

8-T Segment. — Tlie S-T segment shoAA'ed only minor changes after the meal
AA'ith a tendency toAvard depression, although several slight increases Avere ob-
served, too. The depression did not exceed -0.06 mv. in Lead III, Avhile the S-T

: SIMONSON ET AL. : EFFECT OF ME^iLS ON ELECTROCARDIOGRAM 209

segnient remained positive or isoelectric in Leads I and II. Tlie S-T segment
belongs in Group A ol' comparatively stable functions.

TA\avc Amphiude and Direction. — The most pronoiniced and consistent
cliaiiges occurred in the T wave. The T-wave amplitude in Leads I and !!>
2 t, aiid the electrical axis were analyzed. A decrease of the T wave, in at
least one of the limb leads, and usually in all three leads, occurred in all experi-
ments. The decrease of the T-wave amplitude in Leads I, and II, and was
highly significant for all statistical tests used (Table II). The absolute as well
as the percentage diffei*eiico increased in the above order. It can be inferred
that there is also a significant decrease of T.-j. In five subjects with a small
positive Tn before the meal, T^ became small and diphasic after the meal. In
order to decide Avhether tlie T-wave changes sliould be expressed as percentages
of the initial T waves rather tlian in absolute differences, the calculations of
statistical significance were made tor the logarithms of 2 t- It can be seen from
Table II, that the use of logarithms (or percentages) would have no particular
advantage.

T Arrw. — Of 72 experiments, a shift e.xeeeding 2° toward the left was
observed in 40 experimoiils, and a shift toward the right was seen in 16 experi-
ments. Three subjects showed a consistent shift toward the left in all experi-
7nents. The average shift of -5.4° was highly significant for the F (f) -test
and trial variability (F"), but not significant for individual variability (F').
There was iio correlation between the initial T axis and the shift of the T axis
after the meal.

Electrocardiographic Changes After a Iligh-Fat Meal (Series II ). — The
effect of a meal witli 82 per cent fat content was investigated in a total of
24 experiments on 12 subjects. Since only two experiments were available in
each subject, only the Ltest was calculated. Table III sliows the results on some
electrocardiographic functions. All electrocardiographic functions which were
found to be stable after mixed meals (Group A) were also stable after the high-
fat meal, and all functions which showed significant changes in Series I (heart
rate, T wave, alisolute length of Q-T and mechanical systole, ICq_t), showed-
•similar significant changes also in this series. Most of the functions with
frequent, but statistically not significant changes after mixed meals (Group B)
showed a similar response after the high-tat meal. This is also true for 2qrs

■ Table III. Electrocardioorapiiio Change.s After a Meal With High-Fat Content
(Twenty-Four E.xperiment.s on Twelve Subjects)

. ELECTROCARWO-
- GRAPHIC
FUNCTION

MEAN BIFFERENCE

BEFORE AND AFTER

MEAL

t

p*

SIGNIFICANCE

Heart rate

-{•5.96 beats per minute

5.997

0.001

High

Kqt

-10.0124

3.77

0.001 ■

Higli

-fO.0057

1.75

7.05

None

SQRS

-fO.19.3 niv.

5.188

0.09

High

QBS axis

-2.2J°

3,92

0.05

None

ST-

. -0.173 mv.

7.0.32

- 0.001

. Higli

T axis

-4.54°

2.80.

0.01

High ■

*P shows the level of significance expressed as percentage of expected differences; P =
o;oi means that there is only a 1 per cent chance that the. difference is. due to random variation.

210

AMERICAK HEART JOURNAL

and T axis wliicli showed significant changes in Scries I oul,v with the Most.
TJiere was a more ])vononuced tendency to left axis deviation, which was, how-
ever, Jiot statistically significant. Taken all in all, the electrocardiographic
changes after a meal with a high-fat content are about the same as those after
mixed meals.

Elccirocardwgrapjiic Changes (Including Chest Leads) Thirty and Sixty
Minutes After the Meal (Series III). — ^In order to determine the trend of
changes after the meal, in another series (III) the standard leads as well as
CFi, CF2, and CF4 were taken thirh- and sixty minutes after the meal. A total
of 24 experiments were performed on eight suhiects. ^ However, the trials were
not evenly distributed; four repetitions were made in four subjects and Im’O
repetitions were made in another four subjects. For this reason, only the f-test
of significance was used.

Since the meals as well as the subjects Avere the same as those in Series I,
this series may be regarded as a repetition of Series I so far as the tliirtA--
minute interval after the meal is concerned. Thus, Series III affords an oppor-
tunity to check the reliability of the pi’edieted range of least significant differ-
ences for the 5 per cent and 1 per cent lev^els (Table I). We compared the mean
A-alues and the standard deviations of the group as Avell as the 24 indiA'idual ex-
perimenf s. There Avas no significant group difference in any eleeti'ocardiogi’aphie
function between Series I and Series III. In regard to the individual experi-
ments, all values of all electrocardiographic functions Avere Avithin the 5 per
cent range of least significant differences except one value of the heart rate
Avhieh Avas Avithin the 1 per cent range. Thus. Ihe results of both series are in
complete agreement.

There A\-ere only minor differences of the A'arious electrocardiographic func-
tions AA’hen these functions Averc compared at the intervals of thirty and sixty
minutes after the meal. Sometimes the changes Averc someAA’hat more pro-
nounced after sixty minutes ; in other cases. the.A* Avere slightly less pi-onounced
or the same at thirtA'- and sixty minutes. This Avas true for the limb leads as
Avell as the chest leads (Figs. 1 and 2). In no experiment had the electrocardio-
graphic changes disappeared Avithin sixty minutes. Table IV shoAvs that the
mean differences of several electroeardiogra]Ahic functions of Group D are
about the same thirty and sixty minutes after the meal. No fimction shoAved
statistically siguificaiil differences betAvecu thirty and sixty > minutes. This is

Table ia^. Mean DiFcmExcE of Several Electrocardiographic Eungtions Thirty and

Sixty Minutes After the JIeal

PUNCTIOX 1

30 MIN. 1

60 MIN.

. Average heart rate

Mechanical systole duration 0.01 second

QT interval, 0.01 second

SQES (mv.)

axis (degrees)

ST (mv.)

T axis (degrees)

T, CP, (mv.)

T, CP, (mv.)

T, CP< (mv.)

+6.54

-1,87

-0.96

+0.30

-^1.17°

-0.19

-5.62

+0.09

-0.07

-0.24

+7.50
-2.17
-1.12
m.25 -

+1.29°

-0.20

—5.33

+0.06

-0.09

-0.26

SIMONSON ET AL. : EFFECT OF MEALS ON ELECTROCARDIOGRAM . 211

. also true for the individual experiments. Within the 1 per cent range of least
significant differences, there "was only one value of the heart rate, one value of
; the duration^ of mechanical systole, one value of the Q-T interval, and two
vMues of in one subject. All other values were within tlie 5 per cent range.
Obviouslv, tlie range of least significant differences, predicted from experiments
iliii’ty minutes after the meal, is essentially correct also for an interval of sixty,
minutes after the meal.

. The R and S waves of the che.st leads CPi, CPs, and CP 4 .showed frequent,

: but not uniform changes. No Q waves appeared after tlie meal wlien these
waves were absent before the meal. A small Q wave in CP.} in one su))ieci ■

Pig. 1.— Three, standard leads before (a); thl^ minutes after {&). and sixty minutes

:after (o) the meal m two subjects (Sa and Bu). Both subjects show a marked decrease of

the T wave in Leads I and II after tire meal ; in subject Bu, this was more pronounced at
thirty than at sixty minutes after the meal. In subject Sa the positive T wave in Lead ttt
becomes small and diphasic after the nieal. No significant axis shift can be seen. The slichtlv
elevated S-T segment in Lead I of subject Bu is seen to be still elevated after the meal. Sub-
ject Ra has a small diphasic Ps (not common in normal people), which is larger and positive
after the meal. A similar change occurs In P,. .xuu j.ubiwve

212

AMIOllCAN IIEAKT JOUKNAI

remained the same alter the meal. The changes ol the T waves were liighly
significant. In CFi, there was a sliift toward greater i)ositivity, i.e., the nega-
tive or diphasic T wave became Ic.ss inverted or positive (Fig. 2), In CF^ and
CF 4 , the T wave became .smaller, more .so in OF., than in GF-. The values,
differences, variability, and range of least .significant difi'crcneo.s are given in

Lead CR CFg CF4

^F:. ana CPa before (a), thlrly minutes after (b).
f tlie meal m two subjects {Bu and Ca). In Lead CF,, tbc dlpimsie.

1 i^a\e ot supject before the meal becomes progressively positive after the meal: the T
the^meal^in the meal. In bolli subjects tiie T wave tlocreascs after

SIMONSON ET AL. : EFFECT OF MEALS ON ELECTROCARDIOGRAM 213

Table I. -Changes of the S-T segment were minor with a tendency to slight
elevation in OFi and an opposite tendency to slight depression in CF4, but in
no case was this segment deviated below the isoelectric line.

COMMENT

y The experiments show that consistent changes of various fundamental
electrocardiographic functions appear after the intake of moderate meals. Thus,
food intake should be considered as a major factor in the standardization of
the electrocardiographic procedure. The changes are present at least sixty
minutes after the meal, and probably, according to Cardberg, and Olsen, ^
for two or two and one-half hours. The changes might be more pronounced
or more prolonged after hea\y meals, although changes -wathiii the range of
our diets showed no significant differences.

In no case did the electrocardiogram become abnormal after the meal. It
might appear that food intake is of little consequence for the normal electro-
cardiogram in regard to clinical diagnosis. However, this might not be true for
borderline or abnormal electrocardiograms. Experiments on this question are
in progress.

The most important effect of the meal is the decrease of the T Avave. There
was no correlation betAveen the changes of heart rate, QRS axis, or QRS ampli-
tude. Probably the decrease of the T AA'ave might be explained as due to
sympathetic stimulation, as has been suggested for the decrease of the T AA^aA^e
in adjustment tests to A’-ertical position.® A reduction of the coronary blood
flow is not likely to be responsible for the T-AvaA’-e changes . in normal young
persons, since they Avere not associated AA’ith changes of the S-T segment.

SUMMARY

1. The effect of meals on the electrocardiographic pattern Avas studied in
120 experiments on 12 normal young men.

2. The electrocardiograms Av^ere taken before, thirty minutes after, and, in
some cases, sixty minutes after standard mixed meals and high-fat content meals
of^942 to 1,548 calories.

3. The three standard limb leads Avere taken in all 12D experiments, and
in 24 experiments chest leads CFi, CF2, and CP4 AA^ere also taken. The results
were analyzed by precise statistical methods.

4. In the limb leads the significant cha nges obserA'ed Avere an increase of
heart rate, increase of Kqt (i.e,, QT/VP-Pji a decrease of the T AA^aA^e, a de-
crease of the duration of meeh'anicar systole, a decrease of the Q-T interA^al, an
increase of the QES amplitude, and a left axis shift of the T axis.

5. Frequent but not consistent changes Avere observed in the P Avave, range
of heart rate, and E, calculated from the duration of mechanical systole.

6. The P-B and QRS inter A’als, the Q-Avave, and the S-T segment showed
little change.

7. The T AvaA^e in CFi, became more positive pin CFo and especially in CP4,
the T AA'aA'e AA^as decreased.

AAIICRIGAK rnCAUT .JOIJKNAJi

214

■■ S. Tl;e changes produced by the standard mixed meals and the high-fat
meals were similar.

D. The changes observed at thirty minutes after a meal were present with
only minor variations at sixty minutes after a meal.

10. Some practical applications to elect ror-nrdiogra pine ])rneedure are dis-
cussed.

]{ia'Km;N'OK.<

t. Giirdborg, M., and Olsen, lileetrocurdiognifiliic Ciningc.s Tndin'ad Ity (lie Tatung of

' Food, Am. Heart J. 17: 725, lil.'i;’,.

3. Alexander, JI.; .‘Analysts of Variance in Hxporiniontal Human Biology. Jn preparntion.
.'1. Fisher, 3?. A.: Statistical Mctliods for Research ’Worker.*’. Edinburgh, KMfi,

■1. Gouldcn, C. II.: Jitelliod.s of S(ati.>’lical Analysis, New York, 103!*, .tohn Wiley & Sons,
Ine., j). 135.

.5. Kenney, J. F.: Matlioniatic.s of Stidistic.s, Part 2, New' York, JO.'J!', 1). Van Kostrand
Company, Ine.

6. ’YTlson, H. G.: Notes on Annlvsis of Ex])oriin('nl,s Tleplirnted in Tinu', IViomotTies Bull. 1:

lG-20, 304.').

7. Barto, 33., and Btustein, ,1.: Can I’nrialiona in Veiil riciilar S.'^tole Be Itetcrmined From

Electrocardiogram Deflections? .3. Lab. & Clin. Med. 9: 237. 3034.

8. 33arkor, F. .3., Johnston, I*’’. D., and Wilson. F. X.: The Duration of Systole in Hj^po-

calceniia. A^r. JIrart ,T. 1-4: .S3, 1037.

0. Meyorson, IT. S., and Davis, W, 31.; The Tnlbn‘n’*e of Postnie on the Elect rocardiogram.
Am. 3l7:AnT .T. 24: .50.3, 1042.

THE VELOCITY OF BLOOD FLOW IN NORMAL PREGNANT AVOMEN

\ Benmamin Manchester, M.D., P.A.C.P., and Samuel ]). Loube, M.D.

Washington, D. C.

I N 1928, Blumgart and AVeiss’ demonstrated the clinical value of measuring
the velocity of blood flow in health and disease. This has since become
an accepted procedure in the careful evaluation of an indmduaPs cardiac
reserve. The ability to recognize early heart failure by measuring the velocity
of blood flow has now been clearl}’- established. In isolated left ventricular
failure, Avhen the physical signs may be meager, the only evidence of its pres-
ence may be a prolonged arm-to-tongue and lung-to-tongue time. In like man-
ner, it is possible to recognize the imminence or presence of right heart failure
by the prolonged arin-to-tongne and arm-to-lung time, even before the venous
pressure is elevated.

The difficulty in recognizing early heaii. failure in pregnant women, espe-
cially when decompensation occurs in the last trimester, is fully appreciated
by all who have had any experience with this problem. The measurement of
the velocity of blood flow as a means of detecting early heart failure in preg-
nancy has been attempted, but with equivocal results. This has been due to
the fact that the range of normal circulation time in pregnancy has not been
established.

The value for the arm-to-tongue time of normal adults is 9 to 16 seconds
vhen calcium gluconate, saccharin, magnesium sulfate, or decholin is em-
ployed. That for the arm-to-lung time is 4 to 8 seconds, using ether and/or
paraldehyde. There is no evidence that this accepted range applies to the
normal pregnant woman.

- . A search of the literature discloses that there is no unanimity of opinion
as to whether the velocity of blood flow in the course of normal gestation is
increa.sed, decreased, or the same as in the nongraAdd woman. In 1924, Edee^
measiu'ed the blood floAv during pregnancy by the fluorescein method of Koch.^
He found that the circulation time was prolonged to 25.2 seconds in primiparas
and to 23.4 seconds in multiparas (the normal time being 20 seconds). The
greatest slowing of blood flow occurred in the eighth month. Only a single
observation was made on each of 100 women in the final trimester of preg-
nancy. Spitzer,'^ employing decholin and a single determination, found the veloc-
ity of blood flow to be the same in the pregnant' and nonpregnant states/, In a
study reported by 'Oohen and Thomson, 100 determinations, using the cyanide
method of Robb and Weiss, ^ were made on 37 pregnant Avomen. The average
: velocit y of blood floAv, AA>as normal in the first trimester of pregnancy (9 to 21

. ^ From , Garileld Memorial Hospital, and the Department oC Medicine Oenre-P
University School of Medicine, Washln^on, D^ .C. . ueorgre Washington

. Received foi- publication Dec.- 17, 194r>. ^ '• .

216

AMRRICAX IIEAUT .TOUHKAL

seconds), increased in the second trimester of gestation beginning with the
seventeenth week, and remained increased until tl)c thirty-fifti) week, wlien it
again decreased just prior to term. Land! and Bcn.iamin^ employed docholin
in 19 eases and found the velocity of blood flow to be the same in the pregnant
as in the nonpregnant state. Using the saccharin method in 13 normal preg-
nant women, Greenstein and Clahr® found that the circulation time increased
from the eighteenth to the tliirty-eightli week, and decrea.sed in tlie fortieth
week. The apparent discrepancy in tlmsc results i)rojn])(ed tlio present study.

The purpose of this inve.stigation Avas to determine the velocity of blood
floAV in pregnant patients Avithont heart disease: the range of normal, from
the first trimester until the conclusion of gestatioi\.

AIKTIIOD AND MATKRIAI.S

A total of 4S AAwnen Avere examined near tlic beginning of pregnancy. A
complete history and physical examination Avere made Avith the purpose of exclud-
ing any individvial Avitli heart disease. In a fcAv cases, basal metabolism and
blood cholesterol determinations AA’cre made in order to exclude palient.s Avith
hyperthjmoidism. Of this original group, all 48 Avci'e folloAved until the com-
pletion of gestation.

The patients' Aveight, temperature, pul.se, and re.spirafions Acerc recorded
at each examination. Anyone Avith a temperature above 99° F. and/or n pulse
above 120 Avas not examined on that day, hut Avns asked to return on a subse-
quent day. Eaeli patient Avas made to rest in the recumbent po.sition for ten
minutes prior to the determination. The antocnbital A-cin Avn.s .selected as the
site of venipunetiu-e, the same arm being used Avberever possible. Ten cubic
centimeters of 20 per cent calcium gluconate Avas used for tbe arm-to-tongue
time determination, and 0.5 c.c, of a 50 per cent solution of paraldehyde in
ether Avas used for the arm-to-lung time measuremout. The ciro-ulation time
Avas measured by a stop Avatch. The skin overlying the site Avas anesthetized
Avdth 1 per cent noAmcain to allay anxiety and fear of the venipnnclure. The
same observer alAAmys performed the same tc.st on the same patient. Dui'ing
the first feAv visits the patient Avas informed of the end points for both mea.s-
urements and reassured. Only 18- or 19-gauge needles Avere used.

The test Avas performed in the folloAviug manner: With the tourniquet
about the arm, Amnipunctiu'e Avas made into the anesthetized skin. The arm
Avas abducted to a 90-degree angle, the tourniquet Avas released, and no injec-
tion Avas started until the venous congestion in the arm Imd abated. A stop
A\fateh Avas released, and AA'hen the second hand reached the fn'e-second mark,
the 5 c.c. of the 20 per cent calcium gluconate Avcrc injected vapidly {total
injection requiring one to tAvo seconds). Upon the perception of sensation of
Avaimth in the tongue or mouth, the patient indicated bj’ saying “Noav,” and
the time Avas then recorded by the stop AAuteh, after fu'c seconds Avere .sub-
tracted from the total time. After the sensation of heat had subsided, the
arm-to-tongue time determination Avas repeated AAutb tbe additional 5 c.e. of
solution. This Avas done to check on the reliability of tbe subjective response.
An average of the tAvo determinations Avas taken as the final result. In cases

, MANCHESTER AND LOUBE : BLOOD PLd\Y -IN NORM^y:^ PREGNANT WOMEN 217 ; : :

Avhere tlie difference Avas greater tlian three seconds, the results were dis-, ^
carded, and the patient -was requested to return oVi a subsequent day. ; -

After the' measurement of the arm-to-tdngue time had been made, the
syringe was quieldy detached, and the 2 c.c. syringe containing 0.5 c,c. of
ether-paraldehyde was applied to the needle in situ. The stop watch was
released, and, again at the five-second marh; the solution Avas injected quickly
(requiring less than one-half second for its completion). The, end point was
usually objective, and Avas manifested as a short paroxysm of coughing, facial ' .
grimaces, and/or simultaneous-perception of the paraldehyde-ether odor by -
the patient and the examiner. The result -was then recorded as the arm-to-
hmg time.' ‘ - ,

The lung-to-tongue time was obtained by sulffracting the arm-to-lung time •
from the mean arm-to-tongue time.

In this manner, the velocity of blood flov' from arm-to-tongue and arm-rto-
lung was measured every two -weeks from earlj* in gestation until term. Of /
the 73 cases, 48 are available for study and constitute the basis for our obser- . .
vations and conclusions. The remaining 25 eases were discarded because of .
irregular attendance.

Of the 48 patients studied, 13 were between the ages of 16 and 20 years,

31 were between 21 and 30, and four were 31 or older, the oldest being 37
years old. A total of 712 determinations of both arm-to-tongue and arm-to-
lung time vmre made on the 48 cases studied. In the first, second, and third , .
trimesters, 132, 295, and 285 observations were made; respectively. Ten of the'
patients were not examined in the first trimester. In eight case.s of the re-
mainder, only a single determination urns made in the first trimester, and these
were not used in computing the final averages.

In the total scries, there were eleven cases with unpleasant or untoward
reactions. Seven complained of pain along the course of the vein vdien the
paraldehyde-ether mixture was injected. This could always be relieved by the
' ra,pid instillation of physiologic saline solution. In most of the cases the pain ■
had subsided before this measure was applied. Two patients had cellulitis at
the site of the injection ; this was self-limiting and responded to the usual local
measures/ Two had a short but severe paroxysm of coughing, and two experi- :
enced sjmcope. It was observed that these reactions did not occur in the same
individuals on subsequent examinations.

, ■ - , ■RESULT.'S ...

At the conclusion of this study, an evaluation of the results showed that the _

- range of the velocity of blood floAV varied with the trimester of gestation. The
average circulation times for each patient are recorded in Table I. In the first
trimester, the average circulation time from arm-to-tongue. ranged from iO.3
to 15 seconds ; the average , was 12.4 seconds. The' arm-to-lung time ranged .
from. 3.8 to 8.3 seconds; the average urns 6.6 seconds. In the following three ,
months, the arm-to-tongue time was 9.2 to 15.4 seconds, averaging 11.3 seconds. '

, The arm-to-lung. time ranged from 3.8 to' 7.7 seconds ; the mean -was 5.8 sec-

MANCHESTER AND LOUBE : BLOOD BLOW IN , NORMAL PREGNANT WOMEN 219

Table IL Eange and- Avekages of the GikcltAtiox Times in the Three

Trisiesters of Pregnancy *

1 FIRST trimester

1 SECOND TRIMESTER i

1 THIRD TRIMESTER

STUDY

!

RANGE

aat:r-

age

RANGE

Iaver- j
age I

*

RxVNGE

I .AVER-
I AGE ,

1 " ‘ '

Arm-to-tongue

time

10.3 to lo.O

12.4

±1.0

9.2 to 1.5.4

n .3

±1.3

8.0 to 16.2

±10.2 ,

+1.1 .

Arm-to-Iung

time

.3.8 to 8.3

0.6

±0.8

3.8 to 7.7

5.8

±0.9

3.8 to 6.6

±5.0.

±0.7 „

Lung-to-tonguc

time

•i.O to 8.0

5.S

±0.9

4.0 to 8.4

5.5

±0.7

4.0 to 10.3

±5.3

±0.5

•Standard deviations about the means.

Table m. Distribution of Arm-to-Tongue Time ALvll'es in the Three Trimesters

j

.ARM-TO-TONGUE
TIME, SECONDS 1

1 FIRST TRIMESTER |

1 SECOND TRIMESTER

1 THIRD TRIMESTER

NUMBER !
O.F CASES

I’ER

CENT

NUMBER
OF CASES

1 PER

1 CENT

NUMBER j
OF CASES 1

PER ; .

' CENT

14.0 to 16.0

3

10

2

4

1

2

10.0 to 13.9

27

40

37

77

23

48

8.0 to 9.9

0

0

9

19

24

Total

30

too

48

too

48

HDEOMM

trimester, only tAvo average values (4 per cent) fell above 14 seconds, and 19
per cent of the average values Avere less than 10 seconds. In the third tri-
mester, only one arm-to-tongue measurement exceeded 14 seconds, and 50 per
cent of the average values Avere shorter than 10 seconds.

In 45 of the 48 patients, there Avas a doAvnAvard progression of the arm-to-
tongue circulation time Avith each trimester. In only tAvo eases did the aver-
age value obtained in the third trimester fail to be shorter than that obtained
in the first trimester.

• DISCUSSION

Repeated measurements of the velocity of blood Aoav in 48 pregnant AA'omen,
Avho Avere folloAved from early in prcgnanc.A* to tlio conclusion of gestation,
yielded Amlues AA^hich fall Avitliin the accepted range for normal nonpregnant
adults. The mean velocity of blood floAV for the individual patient, as Avell as
for the entire group, shoAA^ed a progressiA'e increase AA’ith each trimester, as
recorded in Tables I and TI. While the OA-er-all range remained the same
throughout pregnancy, the concentration of values for almost the entire group
descended significantly AAnthin the range (Table III). These findings are in
agreement A\nth those of Cohen and Thomson,® Avhose conclusions are based
on a large series of cases.

The clinical value of the measurement of blood floAV is dependent on the
cooperation of the patient, and on the technique (such as rapidity of injection,
size of needle employed, and tj-pe of solution). In addition, repeated observa-
tions assume a clinical significance that cannot be compared AAnth single ob-
servations.

The discrepancies that exist in our results as compared Avith those in the
literature may be more apparent than real. The conclusions made by Klee=
based on the use of the fluorescein method may be due to the method alone,.
By this method, the determination of the velocity is de]3endent on the com-

220

AMERICAN HEART JOURNAL

pletion of the cireulalion after the dye traverses tlie capillary bed. It is well
ImoAvii that in pregnancy the circulation time through the capillaiy bed is
significantly prolonged.^ When corrected for this factor, IClee’s rc.snlts agree
Muth those noted by Cohen and Thomson, and with our own observations.

The differences noted by Spitzer,' Land! and Benjamin." and Greenstein
and Clahr," may be due to the fact that only single observation.s were made
on small groups of patients. Circulation values in the fir.st trime.ster were not
available, and comparable measurements in the subsequent trime.stcr.s of gesta-
tion were not always recorded. Additional evidence that the velocity of blood
flow is inci-eased during pi’egnancy is supplied by Burwell and Strayhorn,"
and Burwell and his co-Avorkers,^“ who demonstrated the decreased arterio-
venous Oxygen difference compared with the increased cardiac output. The
role of the placenta as a modified arteriovenous fi.stula has been discussed,”

The results of the present study indicate that values accepted for non-
pregnant adults are the same as the range noted throughout pregnancy. The
mean value for the group, however, showed a definite increase in velocity.
This fact may bo of clinical significance, for, as shown by Hamilton and Thom-
son,^- the greatest incidence o'f heart failure occurs in the latter part of the
second and the early part of the third tinmester. Heart failure tend.s to de-
crease the velocity and hence to prolong the circulation time. As shown by
this study, the pregnant state modifies this tendency in the direction of in-
creasing the velocity of blood flow. 'When obtained in the second and third
trimesters, circulation values in the upper limits of normal may no longer
indicate an efficient circulation in the pregnant cardiac patient.

SUMMARY AND CONCLUSIONS

Forty-eight pregnant women were followed throughout the three triincster.s
of gestation. The velocity of blood floAV, measuring arm-to-tongue, ann-to-lung,
and lung-to-tongne times, ivas recorded during that period. Throughout preg-
nancy, the velocity of blood flow corresponded with the established normal values
for nonpregnant adults. Beginning with the second trimester, the velocity of
blood flow increased, and the mean values were the shortest in the third trimester
of pregnancy.

The present data indicate that pregnancy modifies the velocity of blood flow
and tends to decrease the circulation times. Circulation time values, therefore,
at the upper limits of the usually accepted normal, may in pregnancy be an early
manifestation, of cardiac decompensation. Such results are of increased signifi-
cance when similar values are obtained on repeated measurements.

REFERENCES

1. Blumgar^ H. L., ana Weiss, S.: Clinical .Studies on Velocity of Blood Blou-. IX. The

of Venous Blood Flo^v to Heart, and
?nv?stfga1io^n 5: 34.^ iS Cardiovascular Disease, J.'Clin.

®’'‘tes in der Schwangerschaft, Ztschr.

3. Koclq^E.^r^^Dio Stromgeschwindigkeit des Blutes, Deut.-^chos Arch. f. Win. Med. 140;

MANCHESTER AND L0U3E : BLOOD FLOW IN. NORMAL PREGNANT WOMEN , 221 ;

4. Spitzer, W,: Die Bliitstromungsgeschwindigkeit in‘ normal er und.gestorter.Sclnvanger-. , .

schaft. Beitrag sur ,Punktionsprufung des Herzens in der Scliwangersckaft imd =
vor der geburt, Areli. f. Gynak. 154: 449, 1933, , . , ’ _ - , . , j

5. Cohen, II. E., and -Thomson, K. Ji: Studies on the . Circulation in Pregnimcy. I. The

Velocity of Blood Mow and Belated. Aspects of the Circulation in Normal Preg-. ■
nant Women, J. Clin. Investigation 15: 607, 1936. .

6. Bbbb, G. P., and Weiss, S.: A. Method for, the Measurement of the Velocity of the

Pulmonary and Peripheral Venous Blood Plow in Man, Am. Heart I. 8: 650, 1933. ,

7. Landt, H., and Benjamin, J. E.: Cardiodynamic and. Electrocardiographic Changes iii ,

, Normal Pregnancy, Am. Heart J.12: 592, 1936. ... , ; ,

8. Greenstein, N. M., and Clahr, J.: Circulation Time Studies in Pregnant Women, Am. :•

J. Obst. & Gynec. 33: 414, 1937. ; '

9. Burwell, C. S., and Strayhorn, W. D.: Observations on the Circulation During and '

, After Pregnancy, J. Clin. Investigation 12: 97,1933. - , , '

10. Burwell, C. -.S., Strayhorn, W. D., Plickinger, D., Cprlette, M. B., Bowerman, E. P., and

Kennedy, .T. A.: Circulation During Pregnane}^ Arch. Int. Med. 62: 97, 1938.

11. Burwell, 0. S.: The Placenta as a Modified Arteriovenous Pistula, Considered in Be- '

lation to the Circulatory Adjustments to Pregnancy, Am. J. M. Sc. 195: 1, 1938:’

12. Hamilton, B. E., and Thomson, K. .L: The Heart in Pregnancj' and the Childbearing '

Age, Boston, 1941, Little, Brown So Company. ,

ACUTE PERICARDITIS IN YOUNU ADULTS

Captain Richakd M. Nat, jM.C., and Captain Nokmak II. Bovnu, M.C.

T he following report concerns tlie clinical eoivrscs of forty-six patients willi
pericarditis. A review of tlic.se cases was undertaken to obtain information
concerning tlic early clinical differentiation between acute pcricarditi.s due to
rheumatic fever and pericarditis of so-called idio]iathic etiology. In addition,
the differential features of acute pericarditis and acute infarction of the myo-
cardium are reviewed.

The patients were studied at one of the Army ’s Rheumatic Fever Centers.
Forty-two patients had had their acute attack of pericarditis in other hospitals
and had been transferred to this hospital at some time during their convales-
cence. Four patients were in this hospital at the time of the attack, or were
admitted during the acute stage.

The patients were all men. Their ages ranged from 18 to 37 3 *eai’S and
averaged 25 years. Thirty-eight patients were in the third decade of life and
seven were in the fourth decade. The diagnosis of pericarditis was made on
the basis of the clinical histoiw, electrocardiograms, and roentgenograms of the
chest. In 29 patients, pericardial effusion was demonstrable by x-ray examina-
tion. In 12 patients, no effusion was detected, but the presence of a friction
rub and electrocardiographic patterns of the type associated with pericarditis
gave adequate proof of the diagnosis. In five patients, x-ray films were not
made during the acute phase of the illness, but the diagnosis was adequately es-
tablished by other evidence. No patients were included in which there was the
slightest doubt as to the presence of pericarditis.

It readily became apparent that the eases studied could he classified into
tliree general groups. In the first group, which comprised the majority of the
cases, pericarditis complicated an attack of acute rheumatic fever. Cases of
acute perieai’ditis which were not associated with any specific etiological factor
con,stitnted the second group. The third group included cases of miscellaneous
etiolog;^’’.

Group 1. Twent 3 ^-five cases of pericarditis due to rheumatic fever consti-
tute Group 1. The average age of the patients was 25.6 years with extremes of
18 and 37 years. Six patients had a liistoiy of previous attacks of rheumatic
fever, two had attacks w'hieh maj- have been rheumatic fever, and one had
chorea. None of the patients were knoivn to have had valvular heart disease
prior to the present attack of rheumatic fever.

In 22 instances, pain in the joints preceded the symptoms of pericarditis.
The time interval between the two varied from 1 day to 3 months, but in 17
cases th e interval was 1 to 12 days. In the remaining five cases, the inteiwals

Received for publication Dec. 3, 1945.

222

NAY AND BOYER: ACUTE PERICxiRDlTIS IN YOUNG ADULTS 223

were 15, 17, 20, 30, and 99 days. The symptoms of pericarditis antedated tlie
joint symptoms in only three instances. In these the time intervals were 5, 6,
and 7 days. ' - . .

In 18 instances, the onset of pericarditis was acute. It was frequently
ushered in hy a ehiU followed by fever and moderate to severe preeordial or sub-
stemal pain. All of these patients noted increase in the pain on deep breath-,
ing, and many had pain on swallowing and on twisting the trunk. Peri-
cardial friction rubs were heard in 14 patients at or soon after the onset of
symptoms. Seven patients had no subjective symptoms of pericarditis except
very mild preeordial x)ain. Two of these patients had a friction rub.

The onset of pericarditis was usually accompanied by a transient leuco-
cytosis; in 20 cases, the white blood cell count numbered 10,000 to 29,000
cells per cubic millimeter. In two instances, the white blood cell counts were
normal (5,800 and 7,450) when pericarditis was diagnosed, and, in the remain-
ing three eases, counts were not made at the onset of symptoms of pericarditis.
In all instances, the leueoeytosis was of short duration; it usually lasted less
than one week.

The sedimentation rates were not altered appreciably by the onset of peri-
carditis. There was a secondary increase from 13 mm. to 32, mm. per hour
(Wintrobe) in one case in which pericarditis occurred three months after the
onset of rheumatic fever. This patient was considered to be in a virtually inac-
tive stage of rheumatic fever at the time at which pericarditis occurred. In
this ease, the sedimentation rate remained elevated for fourteen days.

In 22 cases, x-ray films were taken during the acute stage of the pericaditis
and in 13 instances pericardial etfusion was demonstrated. Electrocardiograms
were taken in all eases. In 17 instances, the patterns were considered to be
diagnostic of pericarditis, and in 8 instances they were suggestive of pericar-
ditis. The specific electrocardiographic changes will be discussed later since
they were similar in all groups.

Six of the ijatients who had pericarditis associated with rheumatic fever
have subsequently developed valvular heart lesions. Four patients have mitral
insuffieienc.Y and a fifth has aortic insufficiency. The sixth patient has mitral
stenosis and insufficiency and aortic insufficiency. This incidence (24 per,
cent) is no greater than that of the patients who developed vahoilar lesions
among the entire group who had rheumatic fever at this hospital.^ Data from
these cases are summarized in Table I.

Group 2 . — ^Fifteen cases of acute pericarditis in which the etiology was un-
determined constitute Group 2. The patients in this group had none of the
stigmata of rheumatic fever either before, during, or after tlie acute episode of
pericarditis. We have designated this type as pericarditis of undefemiined
etiology.

The average age of the patients in this group was 27 years with extremes
of 20 and 37 years. None 'of the patients had any hi.story of previous attacks
of rheumatic fever or chorea. None were Imown to have had valvular heatt
disease prior to their illness, and none had any evidence of vahnilar .le.sions

224

AMERICAN HEART JOURNAL

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NAY AND BUYER; ACUTE BEKICARUITIS IN YOUNG ADL'LTH . 225 '

when exammed. In 12 instances, the onset of pericarditis was extremely ab-
rupt with sudden severe iireeordial or siibstemal pain and usually with chills,
and fever. The pain was aggravated by deep respiration arid by twisting the
trunk or swallowing. The pain was worse in the prone position, and the pa-
tients were more comfortable in a sitting position. Codeine and morphine were
used frequently because of the severity of the pain. The acute symptoms usu-
ally subsided within forty-eight hours. In three cases, tlie onset extended over
a period of three or four days during which the patient noted gradually in-
creasing dyspnea and preeordial pain.

Transient or persistent pericardial friction rubs occurred in 11 of the 15 '
patients. Leucocytosis was -exceptional, and only four of the patients had a
white blood cell count above 9,000 per cubic millimeter at any time during their
illness. The highest counts in these four eases were 12,000, 21,000, 16,000 and
33,000, respectively. ■ In the latter ease, the patient was quite ill and had
nausea, vomiting, and acute nasopharjmgitis. Sedimentation rates were deter-
mined frequently in only nine eases. They were normal in three patients, and
in six patients the highest rates varied from 29 to 78. Increase in the rate
of sedimentation lasted from one to six weeks.

X-ray films of the chest were taken in 13 ease.s, in ten of which pericardia]
effusion was apparent. ‘Frequent electrocardiograms were taken in 14 cases
and were available for review. In each in.stanee, the pattern was considered
to be unmistakably that of pericarditis. The fifteenth patient was in a small
dispensary during the acute phase of his illness and an electrocardiograph was
not available until four weeks after the onset of his illness. At that time, the
electrocardiogi’am was normal. Details of the electrocardiographic patterns,
are discussed below. Data from these cases are summarized in Table II.

Table II. Group 2. Findings in Fifteen Patients With Peric.^kditis of

Undetermined Etioloov

CASE

AGE

(ypvS.)

friction I

RUB

highest

1 WBC

HIGHEST 1

ESR

rERICARDIAl.

EFFUSION

26

21

Present

8,000

Not re-
corded

Present

27

20

Absent

6,750

7

Absent

■ 28

23

Present

6,100

7

Absent

29

29

Present

9,000

42

Absent

.80

24

Present

16,000

78

Present

81

24

Absent

7,500

29

Present

82

21

Present

8,200

40

Present

88

27

Present

12,300

. 51

Present

84

24

Present

21,000

o

O

Present

86

20

Present

83,650

8S

Present

86

00

Present

9.500

84

Present

37

26

Present

Not re-
corded

Not re-
corded

Not talcen

38

oo

Absent

7,600

Not re-
corded

Present®’ ,

89

87

Present,

Not re-

Not re-

Not re-

corded

corded

corded

40

88

Absent

Not re-
corded •

36

Present*

electrocardiogram

stt

■ Diagnostic

Diagnostic
, Diagnostic
Diagnostic
Diagnostic
Diagnostic
Diagnostic
Diagnostic
Diagnostic
Diagnostic
Diagnostic
Not; taken

, Diagnostic

Diagnostic

Diagnostic

A-V TIME

Normal

Normal

Normal

Normal

Norm.ar ,

Normal

Normal

Normal "

Normal

Normal"

Normal

Normal

Normal

Normal

RoentgrenogTams in tliese cases ^vcre not available for revierr, but the reports are quot(

22Q AMERICAN HEART JOURNAL

arotip 5.— This group includes miscellaneous types of pericarditis. One
patient had recurr^t pericarditis with effusion and jileuritis with effusion, one
had pericardial effusion accompanying atypical pneumonia, ^ one had chronic
constrictive pericarditis, one had pericai’ditis associated with an aneuiysm
of the ascending aorta, one iiad pericarditis which followed trauma to the chest,
and one had pericarditis associated with acute glomerulonephritis. These cases
had no common features except the presence of pericarditis.

.ijm, 4127M 5/5m 70M

Fig. 1. — Case 41. Recurrent pericarditis with effusion and pleurisy with effusion. Illness
began on March 24, 1945. The first electrocardiogram, taken April 3, 1945, shows elevation of
the S-T segment in Leads I and 11. Ten days later the T waves were inverted in all leads.
The patient had recovered and Ure electrocardiogram was normal on April 27, 1945. The pa-
tient again became ill witii pericardial and pleural effusions on May 28. 1945. , The features
of pericarditis reappeared in the electrocardiogram on June 10, 1945, .and a normal tracing
was obtained July 10, 1945. T-wave lnver.«ion occurring simultaneously in all four leads was
present in eight cases in this series.

Case 41. — This is the case of a soldier, aged 28 years, whose past liistory included
an attack of pleurisy without effusion in 1935. In • October, 1944, he had an attack of
pericardial and pleural effusion. Spontaneous recovery occurred and he' was returned to
duty. On March 24, 1945, while overseas, he had sudden severe substemal pain and
dyspnea. He tvas admitted to a hospital where a diagnosis of pericardial and bilateral pleural -
effusion was made. Electrocardiograms taken during this episode are reprodticed in Pig. 1.
Characteristic changes, including slight elevation of S-T segments in Leads I and U, fol-
lowed by negative T waves in Leads I, II, and III wore present. T, was diphasic in the
tracing taken on April 13, 1945. The electrocardiogram had returned to normal by April
, 27, 1945. , The patient was evacuated to the Hnited States. On May 28, 1945, he again
became ill with recurrence of the pericardial and pleural effusions. These effusions were
apparent by roentgenography until June 28, 1945.’ Electrocardiograms taken May 31 and
June 10, 1945, revealed changes similar to those of the earlier episode. An electrocardio-
gram taken July 10, 1945, was normal (Pig. 1). No definite diagnosis was made in this
. case. • Culture of fluid removed from the pleural cavities was negative, and injection of
the fluid into guinea pigs revealed no evidence of tuberculosis.

NAY AND BOYER: ACUTE PERICARDITIS IN YOUNG ADULTS . ' ,227

Case 42. — Tlus 2C-year-old soldier developed , pericardial , effusion demonstrated by
roentgenography during the course of atypical pneumonia. A single electrocardiogram,
taken during the first week of the effusion, was normal. Unfortunately, subsequent trac-
ings were not obtained.

Case 43. — Tliis patient had chronic constrictive pericarditis of undertormined etiology.
The electrocardiogram showed low voltage, and T waves were inverted in aU leads, The
liver was enlarged and venous pressure was increased (20 cm. of water).

Case 44. — This 2()-year-old Negro soldier gave a history of a positive serologic test
for syphilis at the age of IS years. The date of initial infection was not known. He was,
admitted to tlie hospital acutely ill and complaining of substernal , pain and dyspnea. A,
friction rub was heard over the precordium. Eocntgenogi-ams and fluoroscopic examination
of the chest revealed pericardial effusion and an aneurysm of the ascending aorta. Electro-
cardiograms revealed serial changes typical of pericarditis. A pericardial paracentesis was
done and 50 c.c. of grossly bloody fluid was obtained. Microscopic examination of the, fluid
revealed no acid-fast or pyogenic organisuns. Culture and guinea pig inoculation of the .
fluid were negative. Eeeovery was rapid.

Case 45. — This 27-year-old soldier was unloading oil drums when he was crushed be-
tween a filled drum and a truck. He was treated in a dispensary but refused hospitalization.
He apparently recovered but two weeks later was taken ill nitli acute pericarditis. The
course of his illness was brief and recovery Avas complete. The role of trauma in this in-
stance is unknown.

Case 46. — This 34-year'Old soldier was admitted to a hosjjital with acute glomerulo-
nephritis. Three days later there were signs of congestive heart failure. A roentgenogram
revealed the presence of pericardial effusion. Electrocardiogi-ams were characteristic of
pericarditis.

Data from these ca.scs are summarised in Table III.

'[’able hi. Group 3. Fintongs in Six Patients With Miscetaaneous Types of

Pericarditis

CASE

AGE

(yrs.)

ASSOCIATED

CONDITION

FRICTION

RUB

HIGHEST

WBC

HIGHEiST

ESR

PERICARDIAL

EFFUSION

ELECTROCARDIOGRAM
STT 1 A-V TIME

41

2S

Bilateral pleural
effusion

Absent

.12,050

42

Present

Diagnostic Normal

42

20

Atypical pneu-
monia

Absent

11,000

36

Present

Normal*

Normal

4.3

22

Constrictive peri-
carditis

Ab.sent

Not re-
corded

49

Absent

Diagnostic

Normal

44

26

Aneurysm of
aorta

Present

8,200

82

Present

Diagnostic

Normal

45

27

Trauma to chest

Pre.sent

13,550

34

Present

Diagnostic

Normal

40

34

Acute glomerulo-
nephritis

Ab.sent

10,400

41

Present

Diagnostic

Normal

♦Only one electrocardiogrram obtained.

ELECTROCARDIOGRAMS ' '

In 43 of the 45 cases of acute pericarditis, electrocardiograms were taken
in .sufficient number and at the proper. time to reveal changes a.ssoeiated with .
pericarditis. In all of these eases, the changes observed in the electrocardio-
grams were diagnostic or suggestive of pericarditis. However, in some in-
stances, only one or two electrocardiogi’ams were taken since the changes noted ■
were sufficiently marked to corroborate the diagnosis. In 29 cases, electro- . .

228

ami'KiOax jii:\K'r jouunal

eardiogx’ams "svere taken at Xrequent intervals until tlie abnormalities liad ceased
to be present. These cases lend thoinselves to detailed review. In many in-
stances electroeardiograms were made at two- and three-day intervals and in none
was the interval longer than one week. A total of 248 electrocardiograms were
studied. The leads taken in all cases included the standard limb loads atid the
apical lead, IVF. The following observations were made.

The earliest eieetroeardiograpjiie abnormality noted wa.s elevation of the
S-T segments. This oecurred in 12 of our eases and disappeared before the
tenth day in all cases except one, in which if was jiresent from the .seventh to the

Mmi lS/7i4i 12/SOlU

The elecUocaraiogn.im of Xov. 18, 19H, was taken during Uie first
Uie a^sepnAfriti or ® Illness. S-T segments In the standaid loads arc elevated,

nnfl -ivave IS concave upward, and T is peaked. On Dec, 4, 1944, Ti, Ts.

and Ta were inverted and three days later, Ts was upright and Ti and Ts were isoelectric. A.

obtained on Dec. 30, 1944. These electrocardiographic changes
are tj-plcal of the pattornq observed In this series of cases. eiuiuf,e!.

thirteenth day. In nine eases, electrocardiograms were not taken until after the
tenth day following onset of symptoms, at which time it is improbable that S-T
segment derangement would be encountered. Tims segmental elevation was
noted in 12 (60 per cent) of 20 cases in which its occurrence could reasonably
be expected. In six of the seven cases in which electrocardiograms were taken
Avithin twenty-four hours of the onset of symptoms, elevation of the S-T seg-
ments was noted. The elevation involved all four leads in two cases, Leads
^I, II, and rV in three cases; Leads I, II, and III in one case; Leads
I and IV in one case ; Leads II and III in one ease ; Leads I and II in two cases ;
Lead n in one case ; and Lead I in one ease. In no instance was there recipro-

NAY AND BOYER: ACUTE PERIC^UKDITIS IN YOUNG ADULTS , , 1 ; 229

cal depression of S-T segments of otlier leads. , In four cases, associated tvith
the ele%^ation of the segments, there was a distinctive peaking of the T waves /
with upward concavitj' of the ascending limb of the wave. Attention, has. been ..
directed to this feature by Barnes,^ and it is well illustrated in Fig. 2.

When elevation of S-T segments occurred, it was transient, and a normal
or near-normal tracing was usually obtained before changes in the T waves oc-
curred. In a few instances the T waves were of veiy low voltage in the one
or two electrocardiograms preceding that in which T-wave negativity occurred.
Striking inversion of the T waves in multiiDle leads occurred in all except two of ,
the cases studied. In eight cases, the T waves in all four leads were inverted^
simultaneously in at least one electrocardiogi’am. In 12 additional eases, T

Pig. 3. — Case 1. The patient became ill with rheumatic fever in November, 1944. On
March 1, 1945, he noted the sudden onset of substernal and precordial pain, A pericardial
friction rub was i>resent. An electrocardiogram, taken Jan. 4, 1945, was normal. Electro-
cardiogram taken March 1, 1945, revealed a slight elevation of S-Ti and S-T: with peaked T
waves in Leads I, II, and IVF. The P-R interval was 0.22 second. The following day the'
electrocardiogram was similar except that the P-R interval was 0.20 second. An electrocardio-.
gram March 3. 1945, was normal. Although electrocardiograms were taken at weekly intervals •
for the five succeeding months, T-wave inversion did not occur. The changes illustrated are ;
minimal. Tills type of electrocardiographic pattern, without T wave inversion, was present '
in two cases in this series. . . '

waves in two or three leads were inverted, and the T waves in the remaining .,
one or two leads were isoelectric or diphasic. Thus, in 20 (65 per cent) of the
cases, the T waves -were either negative, diphasic, or isoelectric in all four
'leads simultaneously. In seven other cases, T-wave inversion .occurred in two
or three leads without significant, changes in the remaining leads, and -in two
eases, no abnormality of T waves was noted. Both of these cases had exhibited

230

AjNIERICAX heart journal

distinctive elevation o£ S-T segments in the earliest tracings and clinically had
unmistakable pericarditis of rheumatic etiologjL

There was a maihed variability in the onset and duration of abnormality
in the T waves of the electrocardiograms in these cases. In 23 eases, inversion
on the T waves was first noted between the fifth and eighteenth days. In the
remaining four cases it occurred in the first, second, twenty -fourth, and twenty-
seventh days. The duration of T-wave abnormality varied from its occurrence
in a single tracing to occurrence over a i)eriod of seventeen weeks ; in 21 eases
T-wave negativity was present for two to nine vreeks. In this connection it is
interesting to note that the electrocardiograms of the patients in Groups 1 and
2 each demonstrated abnormalities for an average period of six weeks. How-
ever, it was observed that in the patients wdth rheumatic fever, T-wave changes
generally occurred earlier in the course of pericarditis and persisted slightly
longer than in patients without rheumatic fever.

Among the patients in Group 2 and Group 3, abnormality of auriculo-
ventricular conduction was not observed. Among the 25 patients in Group 1,
first degree heart block was present in five patients, and second degree block was
present in four other patients. Thus, 36 per cent of patients who had pericar-
ditis of rheumatic origin had conduction defects discernible by electrocai’dio-
graphic methods. These conduction defects were transient in all but two cases.
The first patient still had first degree block with the P-B interval vaiying from
0.24 to 0.28 second fifteen months after the onset of pericarditis. The sedi-
mentation rate remained elevated and the patient had mild joint pains. In the
second patient, second degree heai*t block was present during the acute stage
of the iUness and first degree block persisted for one year. The patient was
discharged from the service despite the defect since he was well clinically and
there had been no change in his condition for the preceding six months.

COMMENT

A comparison of the clinical course of patients in Groups 1 and 2 reveals
that when pericarditis occurs during the course of rheumatic fever, it is
less sudden in onset and the symptoms are less severe than in most eases of
pericarditis of indeterminate etiologjL In our patients, subjective and objec-
tive evidences of joint involvement were invariably associated with pei’iearditis
of rheumatic origin. Indeed, this was the chief point of differentiation. In
.addition, joint manifestations usually antedated those of pericarditis, but in
three instances, were delayed until a few days (one week or less) after the
onset of pericarditis. Another interesting and valuable differential point is
that rheumatic pericarditis usually is accompanied by a moderate leueoeytosis
(10,000 to 29,000) whereas no elevation of white blood cell count occurs in most
cases of pericarditis of indeterminate etiology.

There was no appreciable difference in the occurrence or the amount of
pericardial effusion in the two groups. Neither was there marked difference in
the electrocardiographic findings, except that abnormalities in aurieuloventrie-
ular conduction appeared in nine (36 per cent) of 25 patients who had rheu-

NAYAXD BOYER:

ACUTE PERICx^RDITlS IN YOUNG ADULTS

231

niatic fever. It is worthy of note that in only 24 per cent of patients with
rheumatic fever were there valvular lesions at the time of our last examination.
This is in contrast to the findings of Massie and Levine,® who examined 70 pa*
tients who had had rheumatic fever and pericarditis an average of seven years
previously. Sixty-four per cent of these patients had vahuilar lesions at the
later date. It is possible that valvular lesions will become apparent in our.
patients in future years. The duration of electrocardiographic abnormalities
was approximately the same in the three groups of cases of acute pericarditis.

We have been impressed by the fact that the electrocardiographic patterms
observed in these cases have been highly specific. There has been no con-
fusion of these patterns with the patterns of mjmeardial infarction. We have
not seen S-T segment elevation in the electrocardiograms of patients with
rheumatic fever in the absence of pericarditis. Recently there has come under
obsenmtion a 34-year-old soldier with acute rheumatic fever .whose electrocar-
diograms revealed T-wave negativit}' in all leads. The pattern of serial elec-
trocardiograms was similar to those seen in this series of eases. A friction rub
was not noted during the early stage of the patient’s illness. Roentgenograms
of the chest were not taken, but clinically there was no evidence of pericardial
effusion. With this possible exception, T-wave abnonnalities suggestive of
pericarditis were not found in any patients who had rheumatic fever without
pericarditis in this hospital, although the number of patients in whom a diag-
nosis of rheumatic fever has been made now exceeds 900.

Among the group of 29 patients whose serial electrocardiograms were
studied, there were eight patients in whom the electrocardiograms were nonnal
after the onset of pericarditis. In 25 cases, T-wave abnormalities did not occur
prior to the fifth day. In four cases, characteristic elevation of the S-T seg-
ments was noted in the earliest tracings. Tlie importance of taldng frequent
electrocardiograms is emphasized by the fact that, in our series, normal electro-
cardiograms were obtained as long as two or even three weeks after the onset
of pericarditis.

It is noteworthy that first degree block has persisted in two of our cases
since Massie and Levine reported that, in rare instances, permanent conduction
defects persist for years following rheumatic pericarditis. This occurrence has
not been noted among other patients with rheumatic fever at this hospital.

In general, the electrocardiographic patterns have conformed to those
described by other authors'*'® as occurring in acute pericarditis. Characteristic
electrocardiograms have been obtained, however, in a larger proportion of
cases, possibly because of the large number of tracings which were taken. The
peculiar type of T-wave inversion noted by Bellet and McMillan® occurred in
three eases. This consists of a nearly normal ascending lunb of the T wave to
customary height, followed by a sharp, .straight, descending limb which ends
in a pointed inversion of T wave. This was encountered only in Leads I and it,
and in each instance was associated with rheumatic fever.

Among the patients with pericarditis of indeterminate etiologj’-, there were
three who had been transferred to this hospital, with diagnoses of rajmeardial .

232

AMERICAN HEART .lOUKXAE

infarction. Eight others had heen suspected of having rheumatic fever. The
folio-wing points were found to be especially helpful in differentiation of acute
pericarditis from acute myocardial infarction. In our patients, the age group
was important since myocardial infarction is rare before tlie age of 35 year-s.
The clinical course rvas also suggestive due to the fact that a friction rab is
often heard in the first day in pericarditis, but is usually delayed for sev-
eral days or a week in myocardial infarction. Important subjective symptoms
in acute pericarditis were the aggravation of pain on breathing, svrallo-wing,
and twisting the trunk. These symptoms arc rave in myocardial infarction and
are almost pathognomonic of pericarditis.

In our experience, leucocylosis is uncommon in pericarditis of undclermined
etiology but is usualin myocardial infarction. In patients with pericarditis, the
height of the fever is compatible with an infoolious proce.ss -whcrca.s the tempera-
ture is seldom more than slightly elevated in myoeavdinl infarction, and the ele-
vation rarely lasts longer than three doA-s. Last, the eloclrocardiographic pat-
terns produced by pericarditis may be distinguished from those of myocardial
infarction. The chief electrocardiographic features of pericarditis arc; elevation
of S-T segments without lociprocal doprossion of other segment s; late invemion
of T waves in all of the standard leads and frequently in Lead IV as well; ab-
sence of prominent Q waves in the limb leads; absence of change in B wave in
Lead IV; absence of frequent ventricular cxtrasystolcs; and tiic return of the
electrocardiogram to normal within eight or nine wcelcs in most cases.

SUMAt.Mn'

1. Forty-six cases of pericarditis occurring among young soUliei’s have
been pi*eseiited. In 25 cases, rheumatic fever was the etiological factor; in 15
cases, no definite etiology 'was determined; and in 6 cases, various etiological
factors were present.

2. In tliis series of eases, the important ])oints in tlie differentiation of
acute pericarditis due to rheumatic fever from acute pericarditis of undeter-
mined etiology Avere coincident joint manifestations and Icucocytosis in the
former, and the abrupt, severe onset and absence of lencocytosis in the latter.

3. The electrocardiographic patterns in 43 cases of acute pericarditis have
been rcAueAved. Ele\'ation of S-T segments occurred in 60 per cent of the* cases
in Ariiich electrocardiograms were taken within the first ten days after the
onset of pericarditis. In all Imt tAvo cases, T-ayua'c changes of the distinctive
pattern of pericarditis A\-ere present. The electrocardiograms returned to nor-
mal in four days to seventeen weeks. In eight (30 per cent) of 29 cases in
which serial electrocardiograms were studied, normal tracings Avere obtained
after the onset of pericarditis and prior to the appearance of changes in the
T waAes. This indicates tlie need for taldUg electrocardiograms OA’er a pei’iod
of three to six weeks folloAving the onset of clinical symptoms. No difficulty
was encountered in differentiating the eleetrocardiographic patterns of peri-
carditis from those of myocardial infarction or of rheumatic fever Avithont
pericarditis.

NAY AND BOYER: ACUTE PERICARDITIS IN YOUNG ADULTS .

4. The differential diagnosis of acute nonrheumatic pericarditis and acute
, myocardial infarction has been discussed, and particular refei’ence has been
made to the difference in the electroeardiographie patterns produced by the ; .
two diseases. . - , \ ;

, , , REFERENCES ' , , ■

1. Boyer, N. H. : Electrocardiograpliic Abnormalitie.= in Adults y.ith Rhcuuiatie Fever. ' To
' , , be published. ' '

,', 2. Barnes, A. E>; Electrocardiographic Patterns, Baltimore, 1940, Charles C Thomas.

. ii. Massie, E',, and Levine, S. A.: The Prognosis and Subsequent Bevelopments in Acute '
Rheumatic Pericarditis, J. A. M. A. 112: 1219-1223, 1939.

. , 4. -Noth, P. H., and Barnes, A. R.: Electrocardiograijliic Changes Associated With Peri- ;

carditis, Arch. Int. Med. 65: 291-320, 1940. . ^ ;

5. Bellet, S., and McMillan, T. M.: Electrocardiographic Patterns in Acute, Pericarditis.

Evolution, Causes, and Diagnostic Signiticance of Patterns in Limb and Chest Leads,

A Study of 57 cases, Arch. Int. Med. 61: 381-400, 1938.

■ 6. Vander .Veer, J. B., and Norris, R. F. : The Electrocardiograpliic Changes in Acute Peri-
carditis. A Clinical and Pathological Study.. Air. Heart .1. 14: 31-50, 1937.

THE INCIDENCE OP KHEOTIATIC FEVER AND HEART DISEASE IN
SCHOOL CHILDREN IN DUBLIN, GEORGIA, WITH SOISIE
EPIDEMIOLOGICAL AND SOCIOLOGICAL OBSERVATIONS

Lieutenant CojiMiVNouR. Robert W. Qtunn, USNR

INTRODUCTION AND PURPOSi:

C ONSIDERABLE evidence supports the view that rheumatic fever is now
the most important public health problem in the United States. We know
that, in the United States, rheumatic fever accounts for more deaths than any
other disease in the age group from 5 to 20 years, and moreover, deaths from
rheumatic fever arc on the increase.* Yet these mortality tiguras arc only part
of this problem. The decreased span of life and the economic loss resulting
from the crippling of those who survive make the problem doubly challenging.

These facts have been brought into focus by our recent Selective Sei'vice
figures and the rheumatic fever problem of the Armed Forces. In a re-examina-
tion of 4,994 men rejected for general militaiy seiwiec because of cai’diovascular
defects, rheumatic heart disease was found to be by far the most common cause
for rejection.- Large numbers of men have acquired rheumatic fever for the
first time since entering the Armed Forces. In the Navy it has been necc.ssary
to establish hospitals exclusively for the care of patients with rheumatic fever.
Althougli no exact figures are yet available, it is certain that many of these
patients ndU develop rheumatic heart disease and thus add to the rheumatic
fever problem. Meakius'' believes that rheumatic fever is the primary health
problem in areas inhabited by the white man and states that tuberculosis must
take second place.

It is generally believed that the prevalence of rheumatic fever in tlie trop-
ics and in the southern part of the United States is relatively low. Both PauB
and Hedlejq® however, have pointed to the need for school surveys of heart
disease, especially in the South. This study was undertaken to increase the
knowledge of the prevalence of rheumatic fever.

description op dubein and its school system

Dublin, Georgia, the site of the U. S. Naval Hospital for Rheumatic Fever,
seemed well suited for a survej^ of heart disease in school children since it is lo-
cated in one of the southern states and the school population is composed of
both white and Negro children living in the town or surrounding iniral area.
Dublin is located in Laurens County near the geographical center of Georgia,
at a latitude of 42% degrees and a longitude of 83 degrees. The elevation is
234 feet. The annual rainfall is approximately 50 inches; I’ecent figures were
47.03 inches for 1943 and 50.84 inches for 1944. The temperature is relatively

Received for nublication Oct. 2,5, 1045.

234

QUINN: RHEUMATIC I’T.VER AND HEART DISEASE IN SCHOOL GIHLDREN ' 235

high, with a mean temperature of 58,6° P, for the winter, 66.8° P. for the
spring, 80.1° P. for the summer, and 66.4° P. for the fall. Laurens County
covers an area of 796 square miles and had a population, in 1940 of 33,606.
Among Georgia counties, Laurens Countj’’ is seventh in size and seventh in
population.® In 1945 the population of Dublin w-as approximately 9,000. The
population of both Laurens County and Dublin has fluctuated considerably in
the past two years because of ti’ansient labor and Naval personnel associated
with the building and operation of the U. S, Naval Hospital near Dublin.

The school system of Dublin is composed of three elementaiy schools and
one high school for wdiite children ; and one elementary and one combination
elementary and high school for Negro children. The total enrollment for the
school year 1944-45 was as follows:

WMte
Negro
Total

The enrollment of pupils in the fifth, sixth, seventh, and eighth grades Avas 299
boys and 347 girls, totaling 646. The average daily attendance in these re-
spective grades in the schools for white children wns 367 and in the combined
elementary and high school for Negi'o children was 166.

Of the total number of registered school children in Dublin, 26.7 per cent
were examined. Ho-wever, with the constantly changing school population, per-
haps the average daily attendance gives a more accurate figure of the number
of children available; of this number approximately one-third were examined.
Seventy-two per cent of the total number of children in the fifth, sixth, seventh,
and eighth grades -were examined. Children in these grades w'ere selected
because it was thought that from them an adequate sampling of the age group
in which rheumatic heart disease is most likely to occiu’ could be obtained.
The children selected are beyond the average age of onset of rheumatic fever
(7 to 9 years) ; moreover, they are old enough to exhibit some of the manifes-
tations of rheumatic heart disease should they have acquired rheumatic fever
at an earlier age. It is true that in an older gi’oup of children more of those
susceptible to rheumatic fever would have acquired the disease than in a
younger group. Ho-wever, this number -nnuld probably not be large enough to
change materially the over-all incidence of rheumatic fever or rheumatic heart
disease.

TECHNIQUE

The data used in this study were obtained from school children of the fifth,
sixth, seventh, and eighth grades of both the white and Negro schools. The
form used in recording this data is shown in Fig. 1. After the comsent of the
parents was obtained, groups of 15 to 20 children stayed after school in the
afternoon for examination. A complete histoiy for rheumatic fever -was ob-
tained from the child or parent, followed by a brief general pliysical examina-
tion and a careful examination of the heart. Each child Avas examined un-

Total Enrollment
1,132
722
1,854

Average Daily Attendance
902
596
1,498

23fi

AMi:niC\N III'.AUT .TOUKXAT-

jrAJiE

AGE

HEX

HAOJJ:

Color

Cxtr.

ADDRESS

PARENT’S NAME

P.H. Born:

Kheuinatir i('\pr;

Ac;o:

No of iittnct:-: Pitoo of origin:

<<Bluo biibj-":

Cliorcji .*

Joint R\M‘liing. pain*!, rt'ilnt'*-'! nr tcinlpriK'*:'?:

"Growing pain's":

Noso blcccR:

Fc\or:

Loss of wciglit, K'l'oiU, or failnri- to gain;

Abdominal jiain;

Nodule'S in skin :

Ton'sillitih;

StiPj). FOre tliroat :

Sesulet fever:

DiptliCiia:

Whooping songii;
lloart Di'-eo'-e;

Skin legions:

Exercise tolerani e :

Pulmonary di«e;isi* :

Allergy;

Diet ;

F.ir. Rheimmtis' f.wei-

No. of siblings

Social TlRtoiy,

Home: Where

Number of petFons lising there;

Number of rooms:

Dampnpci :

Financial Flatus:

0 - 1.000
1,000 ■ 2,000

2.000 - ; i,ooo

3.000 - Phm

P.E. Temperature ; PuRo: Rcapiration: Blood Pri'-Rmre:

General dosci iption ;

Lymphatic system:

Sidn:

Respiratory system:

Cardiovascular fcvstoin: Cvanosis: Clubbing: Edema: Cap. Pulse

P.M.X: ■r.C.D: As' Ps l-=t Apical Sound;

Purpura ; Erythema

G.irdiac disease: Cliorea:

Vllergv-;

Country or town;

Murmurs;

Base

L.S.B.

Apex

Intensity

Pitch

Quality

Duration

Time

Es.

Trans.

O.B.C.:

Ecg:

X-ray:

Fluoroscopy :

Impression:

DATE NAME

FIb. 1 .

•QUINI^: KHEUMATIC FEVER AXD FIEART DISEASE IK SCHOOL CHILDREK ' , 237

dressed to tlie waist wliile staiiding, lying on his bach, Ijdng on the left side, '
and Ijdng on the left side following exercise. When a definite diagnosis cotild ■ .
not be made following a single examination, second and third examinations
were made and electrocardiographic, fluoroscopic, and x-ray examinations were .
performed. When a history suggestive of past rheumatic fever was obtained, - ;

' the child’s parents were interviewed and the previous liistorj’’ was either corf ob- ;
Orated or disqualified. \ ’

\ - DESCRIPTION OF MATERIAL . ' . . - f

Of the 401 school children examined, 237 (59.1 per cent) w'ere white and , ■
164 (40.9 per cent) were Negro. No exact figures concerning the racial extrae-
tioii of the wdiite children were obtained, but they were largelj' of Irish and
English descent, their ancestors having settled here three or four generations .
ago. All of the children were born and grew up in Georgia or in the sur- ;
rounding states (wdth the exception of one child born in New York City and ;
Iayo' children born in southern California, none of -whom had rheumatic fever)- ' /
Of the wdiite children, 113 (47.7 per cent) were male and 124 (52.3 per cent).,
were female. / Of tlie Negro children. 41 (25.5 per cent) were male and 123
(74.5 per cent) ivere female (Table I). The average age of the white and of
the Negro children wus 12 %2 years. It is noteworthy that the spread of ages •
ill the Negro group was greater than in the -white group.

tf

Table I. Kumbki;, Kace, and Sex op Children Exahined in the Fifth, Sixth,

Seventh, and Eighth Grades • . '

RACE

1 NUMBER 1

MALE ,

j FEMALE

White

237

113

124

Negi'o

164

41

123

Total

401

154

247 •

fajiily history ; .

A history of rheumatic fever in the families of nine white children ,(3.7 per -
cent) was obtained, but none of the Negro children gave a family history •
of rheumatic fever. The question of family history of heart disease or heart : -
trouble of any type resulted in an affirmative answer from 58 white children ,
(24.4/per cent) and 20 Negro children .(12.1 per Cent). /

, social history

Table II shows that the majority of the children lived ivithin , the ' city
limits of. Dublin, however, 31 (13 per cent) of the white children and 21 (12.8 ,
per cent) of , the Negro children were from rural dirfriets. It was found that ;
crowding existed in the homes of 74 white children (31.2 per cent) ■ and 80 .1.
Negro children (48.7 per. cent). Crowding arbitrarily was said' to. exist when; . .:;

table H. Description OF Homes

'■.• RACE

, . I - , TOWN , 1

RURAL . “ 1

CROWDING

1; DAMPNESS-

,,'Wliite' .
Negro

206(87.0%)
143(87.2%) A.

31(13.0%)

21(12.8%)

, 74(31.2%) ,

• 80(48.7%)

11(4.6%)

16(9.7%)

238

AMERICAN HEi\RT JOURNAL.

the number of persons living in the house exceeded the number of rooms *
During and since tlie building of the U. S. Naval Hospital near Dublin, the
population increase undoubtedl}’ has added to the high incidence of crowding.
Additional housing deficiencies which were i)resent in many of these homes in-
cluded absence of sunlight, dilapidation, fire hazards, inadequate washing and
plumbing facilities, and poor heating.

Dampness was considered to exist when the liome was located near a
swamp or stream, or on low-lying ground where drainage following rains was
poor and water stood under or aroui\d the house for days at a time. Eleven
(4.6 per cent) of the homes of the white children and 16 .(9,7 per cent) of those
of the Negro children were classified as damp (Table TT). The high annual
rainfall makes dampness common in this area.

The economic status of the families of the children is tabulated in Table III.
Estimates of the annual family income were determined from the occupation
or profession of the familj’- provider, the number of working days per year, and
the number in the family contributing to the family income. However, the
figures lent themselves readily to classification in the four income groups shown
in Table III. They indicate tliat low incomes are common in Dublin, particu-
larly among the Negroes.

Table III. Ecoxo.mic Statu.s

INCOME GROUP 1

WHITE

1 NEGRO

Under $1,000 per year

40(16.9%)

101(61.6%)

$l,000-$2,000 per year

98(41.3%)

31(31.1%)

$2,000-$3,000 per year

74(31.2%)

11 ( 6.7%)

Over $3,000 per year

25(10.6%)

1( 0.6%)

RESULTS OP EXAAirNATIO-V

The results of the examination of 401 school children for evidence of heart
disease are tabulated in Tables IV and V.

Prom Table IV it can be semi that 401 ehildreir represent approximately 33
per cent of the available school population. One hundred seventy-six of these
children were classified as heart disease suspects. In this categorj’’ are those
with extrasystoles, functional murmurs, potential lieart disease, and possible
heart disease. They represent 43.8 per cent of all sub.iects, a rate which is
consistent with the surveys of Sampson and his co-workers® Christie,'’ and Samp-

Table IV. Incidence of Congenital and Eheusiatic He.uit Disease in 17C Cardiac
Suspects Pound Among 401 School Children

SCHOOL

POPULATION

EXAMINED

heart

disease

SUSPECTS

i ORGANIC

1 HEART

1 DISEASE

rheu-

matic

CON-

GENITAL

r.ATES PER 1.000
SCHOOL POFUL-VTION

TOTAL]

, %

TOTAL

%

TOTAL

%

TOTAL

%

TOTAL

%

ORGANIC

RHEU-

MiLTIC

CON-

GENITAL

401 1

1 33 '

1 176 '

43.8 '

6

1.5

4

0.67

2

0.33

15

10 i

5

The standard that indicates that dwellings are crowded when they are occupied by more
than one person per room, is commonly used by housing officials and is regarded as a relatively
Wgh standard of measurement. It was used by the Division of Public Health Methods, Na-
tional Institute .of Health, U. S. Public Health Service, In Its National Health Survey in

QUINN : RHEUMATIC FEVER AND HEART DISEASE IN SCHOOL CHILDREN 239

son, Christie, and Geiger,^® and with the consensus of pediatric experience in^
’ dealing wdth childi’en,^^ Cardiac munnurs were found in a large number, 114
(48.1 per cent) of the white children and in 62 (37.8 per cent) of the Negro
children. These were judged to be unexplained or “functional” murmurs and
were all systolic in time. The most common location was along the left sternal
border, the next most common was in the apical region, and the least common
was at the base, in the pulmonary area. Combinations of basal, apical, or left
sternal border murmurs were encountered occasionally. Unexplained murmurs
were heard more frequently in girls, both white and Negro, than in boys.

Six children were found to have organic heart disease, an incidence of 1.5
per cent. Four of these had rheumatic and two congenital heart disease.
Therefore, the incidence of rheumatic and congenital heart disease in the school
population was 1 per cent and 0.5 per cent, respectively. It is interesting to
note that 33 iier cent of the subjects with organic heart disease had congenital
lesions. This is in contrast to other reports,^"’ which gave figures of 10 to
20 per cent, but is consistent with the reports of Sampson et al.® and Sampson,
Christie, and Geiger^® on the west coast.

The children with congenital or rheumatic heart disease and the cardiac
disease suspects were classified further according to the anatomical and etiolog-
ical criteria of the Criteria Committee of the New York Heart Association.^®
The anatomical diagnoses were as follows : coarctation of the aorta, one case ;
aortic stenosis (congenital), one case; mitral insufficiency, three cases; and
mitral stenosis and insufficiency, one case. Four children, two Negro and two
white, who gave clear histories of rheumatic fever but had no physical findings
of heart disease, were classified as having potential heart disease. Two white
cliildren and one colored child who had physical findings suggestive but not
characteristic of heart disease and whose histories did not reveal any definite
etiological factor were classified as havmg possible heart disease.

The rheumatic fever rate was arrived at by including the four subjects
classified as having potential heart disease, from whom histories of rheumatic
fever were obtained, the three eases of mitral insufficiency, and the one case
of mitral stenosis and insufficiency.

The incidence of rheumatic fever and heart disease for both white and
Negro children is shown in Table V. The incidence rate of rheumatic fever
for all children studied was two per cent, for whites 2.1 per cent, and for
Negroes 1.82 per cent. The incidence rate of rheumatic heart disease for the
school population, determined from three cases with mitral insufficiency and
one case with mitraF insufficiency and mitral stenosis was 1 per cent. The rate
of rheumatic heart disease in the white children is 1.26 per cent and in the
Negro children 0.60 per cent.

Table V. Prevalence of Rileumatic Fever and Rheumatic Heart Disease in 401 Dublin,

Georgia, School Children ' - -

1 . white

1 NEGRO ■ , 1

TOTAL

Rheumatic

Rheumatic

Fever

Heart, Disease

0 (2.1%)

3 (1.26%)

3 (1.82%) . - .
1(0.60%)

,8 (2.0%)

4 (1.0%).

240 ' AMi;nic.vx hi^ahi’ joukxal

' DISCUSSION

Factors of possible epidemiological importance in tlie five white children in
the rheumatic fever group were as follows: Crowding was present in one
home. Two children belonged to families with incomes below $1,000 yearly,
and the other three were in the $1,000-$2,000 income group. There was no
family history of rheumatic fever among these ehildi-en, dampness was not
present in their homes, and their diets were, considered to be fairly adequate.
All three Negro children belonged to families with incomes less than $1,000
yearly, crowding was present in one home, dampness wms not present in any
home, there was no family history of rheumatic fever, and the diets of all
three were considered to be inadequate in certain respects.

The incidence of rheumatic heart disease (1 per cent) in Dublin. Georgia, is
moderately high. Although the rheumatic heart disease rate in this community is
not so high as in New England (2.2 per cent) or in Great Britain, it is higher
than that found among the Indians of southern New Mexico (0.5 per cent)^’' and
among school children in parts of northeni California, including San Fi’aneisco
(0.22 per cent) and Kedlands (0.32 per cent).® In a recent .study of the school
children in three climatically ditferent communities of northern California, by
Sampson et al..® definite relations were found to exist between humidity*, pre-
cipitation, and temperature and the incidence of heart disease. Dublin has a
rather high humidity and, a high precipitation, but a warm climate; and, as
might be expected, the incidence of rheumatic heart disease here lies between
the extremes of that of Redlands (0.32 per cent), with a warm dry climate, and
that of Eurelca (2.04 per cent,) with a cool climate and a high precipitation.
It compares closely with the incidence found in Susanville ,(1.09 per cent), a
mountainous community with average humidity and precipitation but vdth
wide extremes of average winter and summei’ temperature. Chavez^® found
that, in Mexico, Avith its diversified but predominantly subtropical climate,
rheumatic heart disease is as prevalent as it is in England and the northern
part of the United States. In view of this observation it is not surprising to
find a rather liigh incidence of rheumatic fever and rheumatic heart disease in
Dublin with its hxunid, warm climate. Sucli important factors in the epi-
demiology of rheumatic fever as low income, croAvding, poor nutrition, and damp-
ness all exist in Dublin and Avould lead one to expect that the incidence of rheu-
matic fever AA'ould not be low. Christie® has pointed out that there is an un-
usually high hospital incidence of rheumatic fever in noifhern California, but
a low general incidence. It would appear that the hospital incidence in Dub-
lin is A'ery low and the general incidence moderately high. None of the chil-
dren Avith rheumatic heart disease or inactive rheumatic fcA'^er had ever been
hospitalized for these illnesses, but three had consulted physicians. This sug-
gests that the clinical manifestations of rheumatic feA'er in Dublin are rather
benign, and agrees with the obseiwation of Seegal, Seegal, and Jost,^® who
determined that the yearly hospital admission rate for rheumatic fcAmr in 24
United States hospitals decreased from latitude region 50 to 45 degrees to
latitude region 34 to 29 degrees. However, the majority of the children in

I ,

QUINN: RHEUMATIC FEVER AND HEART DISEASE IN SCHOOL CHILDREN. ■. 241

Dublin "were unable to afford hospitalization even if “ they had heeded it.
Mills*-® stetes that the disease strikes most frequently in more stormy portions
of the temperate zones and is a more violent form of the infection there.

Rheumatie heart disease is the least common of the four major types of
heart disease (hypertensive, arteriosclerotic, .syphilitic, and rheumatic) v^iich -
occur in the southern part of the United States. This fact is evident 'from ;
both clinical and pathologic studies.^*' As in other parts of southern United
States, in Dublin the incidence of rheumatie fever and rheumatic heart disease
is lower in Negroes than in white persons. No figures are available concerning ' :
the death rate for rheumatie heart disease in Dublin, but according to Hedley"’. :

. the death rates from heart disease were lower, especially for white persons from
5 to 24 years of age, in the Deep South than for botli races in the middle At-
lantic and New England regions.

The number of children included in this study is too small to permit wide ,
couclu.sions to be drawn, but probably a general idea of the status of rheumatic,
fever in Dublin can be gathered from these figures. Larger and more com-
prehensive studies are needed to obtain more extensive information on the inci-
dence of rheumatic fever and rheumatic heart disease in the Southern States..

CONCLUSIONS . ,

1. A cardiac survey of 401 school children in the fifth, sixth, seventh,, and •
eighth grades in Dublin, Georgia, was made.

2. Six cases of organic heart disease were found, giving aii incidence of
1.5 per cent. Of these, four had rheumatic heart disease and two had con-
genital heart disease.

, 3. The incidence of rheumatic heart disease was foimd to be 1 per cent,
for all children examined, 1.26 per cent for white children and 0.60' per cent ^ ,
for Negro, children.

4. The incidence of congenital heart disease was 0.5 per cent.

5. The incidence 'of rheumatic fever was 2 per cent. The incidence in .
white children was 2.10 per cent and in Negi’O children 0.60 per cent.

■ 6. Climatologic and socioeconomic factors such as dampness, crowding, ’

inadequate housing, malnutrition, and low economic status, which are very im- ,
portant epidemiolbgically in rheumatie fever and rheumatie heart disease, were .
found to exist in Dublin, Georgia.

7. Similar but more extensive studies are needed to determine mbre ae- A
eurately the iueidence of rheumatic fever and rheumatic heart disease in diff-
erent' areas of the United States. . • ■ ^

■ , - The cooperation of many persons is necessary in a survey, of this- type. - I, wish to
thank Dr. Amos Clrristie for valuable constructive criticism and suggestions; Gommander' , .;--
B; E. Goodrich, who aided in the examination, of some . of the. doubtful cases; Mr. .,S. H. ,
•Sherman, superintendent of schools for J)ublin,j Hospital .Corps Waves. Iva,' M. 'Barber '
PhMS/c and Edith M. Townsend PhM2/c, who gave yaluable help during the examination
, of thevchildren, and my wife, who gave generously of her time.' ' , . = J

‘ t

242

AMKlllCAN UEAtlT JOUBKAt.

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Clinical Reports

ANOMALOUS OKIGIN OP THE LEFT CORONARY ARTERY FROi\[
THE PULMONARY ART.1-:RY ; REPORT OF A CASE DIAGNOSED
, CLINICALLY AND CONFIRMED BY NECROPSY

S. Bidlow, I\I.D., a2<d Ei.EAXOR R. Macicenzie, I\I.D.

]\IoNTREAL, Canada

T he first recorded ease of a congenital circulatory defect in wliicli the left coro-
nary artery took anomalous origin from the pulmonary artery was described
by. Abrikosoff ^ in 1911, His observation concerned an infant, 5% months old,
who died of pneumonia and who disclosed at autopsj’' a large heart with myo-
cardial fibrosis and aneuiysmal dilatation of the left ventricle. Five years
. Ikter, Heitzmann- reported an identical case and called attention to a striking
similarity to the pathologic findings, observed in adults, which result from
coronary sclerosis or occlusion.

Sanes and Kenny,® in 1939, reporting a case of their own and reviewing
five other' eases with this anomaly, concluded that the clinical features presented
are as typical as are the pathologic changes and deplored the fact that in
none, of the reported cases was an accurate diagnosis made during life. They
suggested that establishment of this circulatory defect as a clinical entity would
make ante-mortem diagnosis more likely. In their opinion the presence of this
lesion should be suspected in patients presenting these characteristics.

A survey of subsequent literature lends some support to this view. A
critical review of seventeen cases by Soloff,"* in 1942, led him to the conclusion
that the majoritj^ of patients with this lesion present a sufficiently characteristic .
clinical picture to make ante-mortem diagnosis possible. On the other hand,
the case reported by Proescher and Baumann® in 1944 did not present clinical
features which readily suggested this anomaly. While the series of- cases is
still too small for the definition of criteria for -accurate diagnosis, all these
observations emphasize the importance of recognizing the occurrence of cardiac
pain in infants and indicate electrocardiographic and radiologic studies as
^'aluable aids in clinical diagnosis.

CASE REPORT

Clinical Sistory (by S. E.). — The patient vas a female infant bom at the Eoyal Vic-
toria Montreal Maternity Hospital on Eeb. 17, 194:5. Delivery -was at term .and. was entirely
■ normal. The family includes two other children, the younger of which, aged 5 years, suffers

From the Department of . Patholog^v Children’s Memorial Hospital, and the Denarlmpht
of Pathology of McGill University.

Received for publication Oct. 15, 1945. ‘

243 .

ajij:ricax iikart journal

244

from broncliial asthma; the older child is nonnal. The father is alive and active. The mother,
33 years of age, has enjoyed good health except that for the past five years, she has snlTcred
from amenorrhea, going as long as two years without a menstrual flow. She consulted mo on
Sept. 14, 1944, hecau«6 of an abdominal mass. IVlicn told that the abdominal tumor was
indeed a piegnancy, she expressed a fear that, bceause conception had occurred following a
period of amenonhea of about three months' duration, nonnal fetal dc\elopment wa.s unlikely.
I assured her that this was not the case and that her fears were unfounded. However, im-
mediately after delivery, I was called to sec the newborn infant and thus had the ojjportunity
of examining her at the age of only two days.

Examination at this time revealed an apparently normal infant. There was no i-yano^is.
The heart was not enlarged and no murmurs or abnormal rounds were heard; the rhythm wa‘<
normal, and the rate was 150 per minute. The lungs W’orc resonant throughout, and no rfiles
or abnormal breath sounds were audible. 1 felt justilicd in reassuring the mother that there
was no evidence of any anomaly. Dr. S. B, Shapiro then look cJinrgc of supervising the feed-
ing and general care of the baby.

JPlg. 1. — ^X-ray film shows heart enlarged to the left and also to tlie right. Its middle
left border Is very rounded. There Is evidence of partial atelectasis of the upper lobe of
the right lung.

t

I saw' the infant for the second time on May 24, 1945, because of peculiar paroxysms
observed by the nurse who bad been caring for the infant since May 10. She had been told
that the patient was a normal and healthy infant; however, she noticed that the baby rarely
ate well and seemed uncomfortable while taking her feedings. After taking 'about an ounce
of formula, she w’ould seem to choke and to have difdcnltj^ in breathing and tlion would rest
for several minutes before resuming her feeding. Small frequent feedings were therefore
resorted to. There was a good deal of wheezing, but vomiting was not a feature; the infant
was restless at night. During these two weeks, the nurse had observed five paroxysms of
‘ ‘ shortness of breath, rapid pulse, flushed face which turned blue and then wliite, and profuse
perspiration,” These attacks lasted from four to eighteen minutes, and left the infant ex-
tremely weak. Dr. Shapiro was notified. He ordered an x-ray film of the chest, and, because
of the history of bioncliinl asthma in the family, adopted treatment on the basis of a possible
allergic manifestation. <

KIDLOW AKD JL\CKEXZIE; ANOMALOUS ORIGIN OF LEFT CORONARY ARTERY 245

Examination at this date revealed a 3-month-oId infant, who apparently was -normal' .
. in mental and physical development. The skin and mucous membranes were pale/ but there .
, ' was no cyanosis or clubbing of the fingers. The lungs were resonant throughout and no -
rfiles or abnormal breath sounds were heard. The heart, on percussion, revealed an increas'e
in the area of cardiac dullne.«s; the sounds, however, were normal and there were no.murmursy ,
tlie rhythm was normal and the rate was 1.50 per minute. Posteroanterior and lateral x-ray
. Mms of the chest made at this time showed cardiac enlargement both to tlie left and to the
right; the middle portion of the left border was unusually rounded. Partial atelectasis of the
^ upper lobe of the right lung was also disclosed (Pig. 1). • .

Fig. 2. — May 24, 1945. Normal rRythm. Rate, 160 to 167. P-R, 0.12 second. QRS,
0.06 second; Normal axis. S-T interval depressed in Leads I and II. Inverted T in Leads
I and II; upright T in Lead IV. Diphasic QRS in Lead III.

The account given by tlie nurse of acute discomfort brought on by feeding, . and, of
.paroxysms of dysj?nea, cyanosis, pallor, and sweating in the presence of a large heart, brought
' to mind the possibility of cardiac pain on the basis of an inadequate coronaiy blood, supply, '
and I recalled reports in the literature of cases presenting, a similar clinical picture. I took
an electrocardiogram, wliich showed inversion of T waves in Leads I and II, no axis deviation, ,
and an upright T wave in Lead IV (Fig. 2). This electrocardiogram was typical of coronary' :
, artery disease in the adult. .

,, iTOpfmion-.—- Episodes suggestive of cardiac pain, provoked' by the' effort of 'feeding and
accompanied by dyspnea, cyanosis, pallor, and'sweats, in. the presence of an - enlarged heart "
together ivith an electrocardiogram showing, inversion of T waves 'in Leads. I and 11, indicate,"

, an inadequate arterial blood supply to the heart ^muscle and constitute; a syndrome strikingly '■
.suggestive of the. clinical effects produced by anoihalpus origin of the .left coronary artery,
from the pulmonary' artery. < • , - ' '! '■ ' . .. .

246

AMEKICAN riKABT .lOUftNAb

Juno 20.— Since my precedinR visit the distre.ss ncconipnnying foedinR had become
progroBsivGly worse; there was a good deni of wlieoring and the paroxysins previously de-
scribed were occurring even during rest. Evmninntion revealed no new findings, except that
the rate of increase in weight was retarded because of the difiiculty in feeding; the heart
appeared larger tlian on the previous cxnininafion four weeks earlier.

The infant appeared bright, happy, and playful and throughout the examination kejit
smiling and cooing. But no sooner had the examinaiion been completed than a sudden change
came over her. The patient developed an anxious look and her eves winred -harply 0“ though
she was in great pain. She attempted to cry. but tbo effort apparently added to her agony,
and what might have been a erving sjioll broke up into a succeasion of abort respiratory
grunts. She remained immobile. 'J’licre was dyspnea, tachycardia, eyanoais, and (hen pallor,
resulting in an ashen-graj' countenance; perspiration stood out in beads on ber forehead.

Fig. 3. Fig. 4.

Fig. 3. — -RlgJit vcntiicle opened to show tie- oilOce of the anomalous corenarj- vc'.ael
abov’e the posterjor cusp of the pulmonary valve Xote the nonn.al appearance of t’h*' rlgtit
ventricular myocardium and endocnidlum.

Fig-. 4. — Ijcft ventricle opened to show the ample eoronao orifice above tlie anterioi
aortic leaflet. The Abiotic appearance of Uic Inner halt of the myocardlvim may be seen. The
hypertrophy of the wall and dilatation of the chamber are obvious ns Is the thickening of the
endocardium.

A profound tuuislormation had occurred; the placid infant of only a few minutes before
had taken on the expression of a wizened old woman. The attack lasted eight minutes and
left the infant completely limp, her entire body covered with cold sweat.

The paro.xj'sin I had just witnessed was similar to those often observed during the
acute phase of a coronary attack. There was no question in my mind that ray little patient
had just experienced a severe attack of cardiac pain.

June 26.— The temperature rose to 101” P.; the patient developed a cough and a nasal
discharge. Dr. Shapiro found signs suggesting pneumonia.

June 27.— The temperature loso to 103” F. X-ray oxaminntion confirmed the nresonec
of pneumonia. The patient died at f,;45 P.W.

EIDLOW AND ilACKENZEE : ANOMALOUS ORIGIN OP LEFT CORONARY .ARTERY 247

Clinical Diagnosis, — (1) Anomalous origin of the left coronary arterj'^ frotti the pul-
monary arteiy; (2) pneumonia.

Pathologic Findings (by E. B. M.) . — A necropsy was performed three hours after death
at the Cliildren ’s Memorial Hospital. The body was that of a moderately well-developed and
well-nourished female infant, presenting no notable external abnormalities. On opening the
thorax, the heart presented tremendous enlargement to the left and practically obscured the
left lung. The riglit upper lobe was completely atelectatic and the right middle lobe was
markedly emphysematous. Patchy areas of pnemonic consolidation were present in the left
lung and in the right lower lobe.

Pig. 5. — Photomicrograph (XlOO) of left ventricular myocardium showing extensive fibrosis.

Further examination of the lieart revealed dilatation of both ventricles and auricles,
but particularly of the left ventricle. The weight was 85.3 grams as compared with an average
normal for this age of 27 grams. The measurements of the heart were: mitral valve, 5.1 cm,;
aortic valve, 2.8 cm.; tricuspid valve, 5 cm,; pulmonaiy valve, 4 cm.; left ventricular wall,
0.2 to 0,8 cm. ; and right ventricular wall, 0.1 to 0.2 centimeters. The ductus arteriosus was
closed. The right coronary artery arose in its usual manner from the sinus of Valsalva of the
anterior aortic leaflet and followed the usual course of the normal right coronary artery to
supply the right Ventricle and a small part of the right border of the left ventricle. No
coronary artery orifice was present above the left posterior cusp. The left coronary arterj'
arose from the pulmonary artery in the sinus of Valsalva just above the posterior cusp' of the
pulmonary valve and thence pursued its normal course to divide into a circumflex branch and
an' anterior descending branch. This vessel supplied the left ventricle alone as far as could
bo determined by dissection with fine scissors. ^ .

The left ventricle presented hj^^ertrophy of its walls, and on section the inner third :
of the myocardium was gray and fibrotic in appearance. The chamljer was markedly, dilated.

AMERICAN HEART JOURNAL

' 248

The endocardium of the left ventricle was thickened and opaque throughout. The myocardium
and endocardium of the riglit ventricle appeared normal (Figs. 3 and 4). .

Histologic examination revealed fairly extensive scarring of tlxc Tnyocataium ox tlie left
ventricle, particularly of the inner half, associated with atrophy and vacuolation of the muscle
fibers. The endocardium was tliickened and fibrotic. No embryonic sinusoids were present.

The smaller coronary artery branches showed slight thickening of the media of the vessel
wall by scar tissue, but no endarteritis obliteians was pioscnt (Fig. 5).

Other viscera presented no abnormalities.

DISCUSSION

111 six of the eases recorded in the literature, individuals with this anomaly
have attained adult life. Abbott’s® case concerned a woman, 64 years of age,
who died accidentally. At autopsy it was found that the descending branch of
the left coronary artery expanded into a large sinus, 2 cm. in diameter, which
communicated with thick-walled vessels behind it. The most recent record' of
an individual reaching adult life was that of a man 30 years of age. Autopsy
in this ease revealed no myocardial fibrosis, a phenomenon which wa,s attributed
to a compensatory arterial supply by the right coronaiy arteiy, as demonstrated
by a dilatation of the right coronary artery and by aceessoiy distribution of the
distal end of tlie right coronary beyond the interventricular septum and into the
ventricular muscle; the area normally supplied by the circumflex branch of
the left coronary arteiy. However, such remarkable anastomoses between the
coronary arteries, or between the left coronaiy artery and the left ventricular
cavity, do not occur in the majority of cases with tliis eireulatoiy defect;
death within the first year is therefore the usual outcome. The recognition of
tliis anomaly during life is therefore very important from the point of view
of prognosis, so that expectation of life and serious impending consequences may
be fully appreciated.

The case here recorded confonns in its clinical features to those presented
by the majority of the cases reported. The clinical diagnosis was based on
paroxysms of cardiac pain suggesting angina pectoris, marked enlargement of
the heart, and an eleetrocardiogz’am of the type associated with coronary artery
disease. A search of the literature yields very meager information regarding
electrocardiographic studies. The only electrocardiogram on record is tlie one
taken by Bland, While, and Garland® in a patient who revealed this circulatory
defect at necropsy; the tracing showed a normal axis with inversion of T waves.
On the other hand, the electrocardiogram of a patient with idiopatliic congenital
hypertrophj^ of the heart® was normal. Full use was made of this information.
The electrocardiogram of our patient closely resembled that taken by Bland
and bis co-workers, and helped considerably in the differential diagnosis.

Pulmonary atelectasis, a feature of this ease, has been recorded in other
cases and is probably secondary to the hypertrophy and dilatation of the heart.
It IS worth noting that, consistent wdth the majority of cases reported, our
patient appeared normal at birth. No adequate explanation has thus far been
advanced to explain the absence of symptoms during the early weeks of life.
One may speculate that the blood supply to the myocardium may be adequate
when activity is at a minimum. Another explanation suggested® is that a slight

EIDLOW and’ JIACIOENZIE : ANOMALOUS ORIGIN OF LEFT CORONARY ARTERY 249

patency of the ductus arteriosus, which may have escaped occlusion in the early
weeks of life, permits a mixture of arterial with venous blood in the pulmonary
artery. . .

. SUMMARY '

A case is presented of anomalous origin of the left coronary artery from
the pulmonary artery in which the condition was diagnosed during life. The
diagnosis was made on the following observations: paroxysms of cardiac pain
characterized by .sweating, pallor, cyanosis, and dyspnea; great enlargement
of the heart both clinically and by x-ray examination; and electrocardiograms
showing inversion of the T waves in Leads I and II. These constitute a S3m-
di’ome indicating inadequate arterial blood supply to the heart muscle. The
clinical diagnosis was confirmed by necropsy which revealed a left eoronaiy
artery arising from the pulmonaiy artery and suppl.ving the left ventricle alone.
No anastomotic coronary circulation existed.

REFERENCES

1. Abrikosoff, A. : Aneurysma des linken. Herzventrikel.s mit abnornier abgengstelle der linken

Karonarterie von der Pulmonalis bei einen funfmonthcbin Kinde, Virchows Arch. f.
path. Anat. 203: 413, 1911.

2. Heitzmann, O.: Drei Seltene Falle von Hcrzmissbilding, Virchows Arch. f. path. Anat.

223: 57, 1917.

3. Sancs, S., and Kenny, F. E.: Anomalous Origin of Left Coronary Artery From the

Pulmonary Artery, Am. J. Dis. Child. 48: 113, 1934.

4. Soloff, L. A.: Anomalous Coronarj' Arteries Arising From the Pulmonary Artery, Ail.

Heart J. 24: 118, 1942.

5. Proescher, F., and Baumann, F. W.: Abnormal Origin of Left Coronary Artery With

Extensive Cardiac Clianges, J. Pediat. 25: 344, 1944.

6. Abbott, M. E.: Congenital Heart Disease, Osier’s Modern Medicine, Philadelphia, 1928,

Lea & Febiger, vol. 4.

7. Euddock, J. C., and Stehly, C. C. : Anomalous Origin of Left Coronary Artery Prom the

Pulmonaiy Arterj’-, U. S. Nav. M. Bull. 41: 175, 1943.

8. Bland, E. P., Wliite, P. D., and Garland, J.: Congenital Anomalies of the Coronary

Arteries: Report of an Unusual Case Associated With Cardiac Hypertrophy, Air.
Heart J. 8: 787, 1933.

9,. Sprague, H. B., Bland, E. F., and Wliite, P. D.: Congenital Idiopathic Hypertrophy of
the Heart, With Unusual Family History, Am. J. Dis, Child, 41: 877, 1931.

COMBINED SULFONAMIDE AND DIPHTHEEITIC MYOCAEDITIS
IN CUTANEOUS DIPHTHERIA

Ralph C. Orkkni:. ]\r.D.

]\Ikmimiis, Tkn'x,

A LTHOUOH mentioned in all standard works, ('iitnneons diphtheria with
^ resiilting fatal myocarditis is rarely seen in modern practice. Since the
onset of this war, only a few reports, not yet prepared for }ml)lication, have
appeared from military .sources. The purpose of this paper is to place on
record a case in which the myocardial damage of diphtheria toxin was com-
bined with an inflammatory lesion caused by .sulfonamides.

REPORT or A CASK.

A 21-year-old soldier, who had been in the service for thre.c years, was
admitted to our station hospital in England on Nov. 15. 1043. several days
after having been transferred from Sicily. He complained of epigastric pain,
dark urme, clay colored stools, aiiorexia, vomiting, and a mild cough. All of
these symptoms had been present for one week. Four days after this onset,
he developed generalized icterus and the other symptoms abated. He stated
that three weeks previou.sly he noticed a lesion having the appearance of a
small abrasion approximately 1/4 inch long on the middle phalanx of the right
index finger. This had become larger, until, on admission, it was an eleva-
tion % inch in diameter and slightly tender. It was covered with epithelium
with no break in the skin surface. The patient was not aciitely ill. His tem-
perature and pulse were normal. ITis skin was deeply icteric. The liver could
be felt 1 fingerbreadth below the co.stal margin and was tender. The spleen
could not he felt.

The patient was put on routine icterus therapy, consisting of a high-
carbohydrate, low-fat, high-vitamin diet with bed rest. A surgical consulta-
tion was ordered. After examination, the surgeons repoi’ted a .spi'eading
infection with lymphangitis, which in several days was tender and palpable.
The Ruetuant mass was incised and only a thin serous fluid exuded. Hot wet
dressings were applied. Two days after incision the patient’s temperature
rose to 103° P. and the right axillary nodes became more tender and swollen.
Despite the administration of 1 Um. of sulfadiazine every four hours for nine
days, the cutaneous lesion did not heal ; the adenitis persisted and he continued
to run a septic course. On Dec. 1, 1943, two Aveeks after his admission, and
five weeks after the' skin lesion was noticed, the patient suddenly developed
clonic convulsions and lost eonseionsness. The pulse was regular and feeble.
but the rate wms found to he only 17 per minute. The systolic blood pre.s.sure

KccelveC for publication Oct 2. 194.^.

250

^ - GKEENJ5: COMBINED ; SUEFOXAailDE -ANI) DIPHTHERITIC iAIYOGARDITIS : .. '251

; was 70 min. and the diastolic pressure could Hot be oBliaihed. In a few min- ;■
utes he regained consciousness. Although he Avas ratiohal and oriented, his ;
skin was cold' and clammy; he, was cyanotic,' and the heartbeat continued to ;
be slow. ‘ ' ' . ; - . . - ^ ; v : ■

Electrocardiograjphic studies revealed an auricular rate of 120 and .a. ven- ,
tricular rate of 30: There was complete ’A-V block. The axis was deviated to. ■
the left. The duration of the QRS complex was 0;14 second. The P waves; :;
were upright in Lead I and diphasic in Leads II and III. The QRS complexes
were slurred in all leads and described as being of the “S” type in Leads I, ,
II, and III. The T Avaves Avero upright in the three indirect leadk A chest
lead, taken at Position 4, shoAved an initial upAvard deflection followed by an. -
inverted T AyaA’'e. . A

The .smears and cultures of the discharge from the skin lesion reAmaled ;
diphtheria bacilli, the Adrulence of which Avas later confirmed by animal an-
oculations. The AAkite blood cells were 15,450 Arith a normal differential.;',
count. During the next feAv days the patient’s pulse rate Aaried betAveen 39.
and 60 and the blood pressure Avas approximately 100/60. fSixty thousand
units of diphtheria antitoxin were administered immediately after the diag-
nosis of diphtheria was made. The patient Avas given adrenalin and ephedrine '
in small doses, but he remained extremely Aveak and cyanotic Avith cold p>ers-
. piration and severe nausea. His pulse reverted to a regular rate of 30 two ■
days after the first Stokes-Adams seizure. The first heart sound Avas noted
to be A^ery variable in intensity. Again, during this day he suddenly developed
generalized clonic convulsions, became comatose, and expired.

Post-Mortem Findings. — Autopsy, tAvo hours after death, disclosed that the ,,
index finger of the right hand Avas markedly SAvollen and covered by a bluish .
mottled discoloration and epidermal desquamation. Over the middle portion
■ of this area Avas an unhealed inci.sion encrusted Avith old blood. The axillary'
lymph nodes Avere enlarged to pea and almond sizes.

' The heart Avas of normal size and AA^ight Avith no obAHOus softness. The;.

;; myocardium appeared normal on gross examination. The coronary arteries: ;
AA'cre -patent and shoAved no eAudence of sclerosis.

, T^^ lungs were crepitant throughout. Some frothy exudation was seen ■
on the, cut surface. ' ■ • . ' , . ;

The liAmr was enlarged and about 50 per cent heaAuer than the noriffal.
-It was distinctly darker than u.sual upon the external and cut surfaces. The .

. hepatic lobulation Avas increased in distinctness. There were' no . areas, of de-
discoloration. ' .

, The glands surrounding the anterior .fold of the epiploic foramen AA^re
. greatly enlarged and measured 1. to 2 cm. in diameter. They were soft and'

" , elastic in consistency. Their cut surfaces shoAved an increased prominence /
V.; of .the lymphoid foRicles. ' .

. The'spleen Avas enlarged to tAAuce its usual size and Avas firm in consistency. ■
; '; ,The capsule. Avas tense and of a dark slate blue color. The cut surface shoAved
; normal markings. The pulp scraped easily and was dark fed, and velvety in,' ^
appearance. The. splenic arteries and veins- Avefe patent. - ' ■ . ' L ' T

252

AMERICAN HEART JOUUNAIj

Fig. 1. — Cutaneous losion

showing fatso niemhrane anti 'l)actcrlal
Aledtcol Museum, Negative 87710.)

colonies.

(U. S. Army

Pig. 2 — Granulomatous interstitial lesions, low power. (V. S. Army Afedical Aluseum Nega

tive 87713.)

aUEENE: COMBINED SULFONAMIDE AND DIPHTHERITIC JIYOCARDITIS .253

Fig. 3A. — Granulomatous insterstitJal lesion, high power. Note the large pale mono-
nuclear cells characteristic of “sulfa” medication. (U. S. Army Medical Museum, Negative
87714.) ■

F’lg. . 3B. — ^Myocardial interstitial lesion,
j.re characteristic of sulfonamide myoca-rditis
i7711.)

high power. The IsLrge
. fU. S. Army Medical

mononuclear cells
Museum, Negative

254

AlklERICAN IIEAKT JOURKjUj

The mesenteric lymph nodes were enlarged to almond size and in all re-
spects resembled those seen surroiinding 'the bile ducts in the anterior fold
of the epiploic foramen.' . . , ■ ' . ■ ■ .

Fig. 4.— Myocardium, sliowlng diffuse lesion with degeneration, frngjnentation, and interstitial
infiltration. (U. S. Army Medic.al Museum, Negative S7712.)

Microscopic Ohservations. — A section through the cutaneous lesion in Uie
right index finger shoAved ulceration, hemorrhage and an acute inflammatory
exudate containing numerous polymoi’phonuclears. Many collections of blue-
staining bacterial colonics could be seen on and near the surface. Under liigher
poAver these Avere revealed to vary in size and to be rod-shaped and trans-
Amrsely banded, Avith a tendency toAA'ard clubbing.

A section through the right ventricle of the heart shoAved diffuse cloudy
SAvelling. Simple necrosis, Zenker's necrosis and granular degeneration of the
myocardium Avere present in various aheas. hlany of the cardiac muscle fibers
Avere replaced by ncAv fibrous connective tissue and others Avere broken up into
hyaline masses. The interstitial tissue contained an infiltration of large mono-
nuclear cells Avith a smaller proportion of polymorphonuclears. ■ Slany of these
mononuclears Avere large and pale and contained eosinophilic cytoplasm. Their
nuclei Avere large and A'^esicular. Section through the Avail of the left A'entriclc
revealed a more striking picture AAith . greater necrosis and fragmentation of
th6 heart muscle and the interstitial infiltration being so marked as to con-
stitute a granulomatous lesion.

There Avere considerable bilateral pulmonary congestion and atelectasis,
Avith mononuclear infiltration and thickening of tlie alAmolar septae. There
Avei’e numerous pigment-laden macrophages in the ah’^edli.

GREENli: COMBINED SDXFONAMIDE , AND. DIPHTHERITIC MYOCARDITIS ' 255.,

The liver sections showed Varying degrees of centra] atrophy and degeh- ;
oration and considerable congestion of the eentral, vein and sinnsoids. The*
portal spaces contained a heavy infiltration Of roiind cells and polymorphonu-
clear leneoeytes. .

The germinal centers of the spleen showed enlargement and early focal,
necrosis. There was a reticulo-endothelial proliferation in the follicles. ^ The-
splenic sinusoids were dilated and congested with red blood cells. The eh- '
larged lymph nodes also showed reticulo-endothelial hyperplasia in the germi-
nal centers as well as in the intervening medullary cords. Many polymor- ;
phonuclears were present in the sinusoids.

The anatomic diagnoses were: cutaneous diphtheria and wound of the
right index finger; acute diphtheritic and .sulfonamide myocarditis; acute. infec-
tious hepatis; pulmonary edema and atelectasis; acute toxic mesenteric lym-
phadenitis ; and chronic passive congestion of liver and spleen.

COMMENT

Ohin and Huangy in their definitive review of the literature, report that
the majority of investigators of diphtheritic myocarditis find mainly an in-
volvement of the cardiac parenchyma. Others, however, report an interstitial
inflammation. There is no united opinion regarding the sequence of these
changes. Most consider the interstitial changes to be a reaction secondary
to the parenchymatous lesion, with the inflammatory cellular reaction and con-
nective tissue proliferation limited to areas where the myocardium is under-
going necrosis. Cases, how^ever, have been reported of independent interstitial,
inflammation, unassociated with' a parenchymatous lesion.^’

Burkhardt, Eggleston, and Smith,® who studied 140 cases of diphtheritic
myocarditis, found that 28 had electrocardiographic changes. Fourteen of
these died, even though large doses of antitoxin were administered, on or
before the fourth day of illness. - All of these patients had conduction changes, .
eleven being auriculoventrieular dissociation. Only three patients Avith con-
duction changes survived, and all with auriculoventrieular dissociation suc-
cumbed. They report histologic changes progressing through edema, conges-
tion, cellular infiltration, degenerative changes and fibrosis.

A hew t 3 q)e of interstitial myocarditis, has been reported recently by,
French and Weller.^ They found that out of 283 patients who recen’-ed large :
quantities of sulfonamides and later came to necropsy, 126 had myocarditis.
There wus a perivascular and diffuse infiltration wuth large clasmatocytic mopo-
nuclears and other cells ivith granular acidophilic cytoplasm. A similar tjqoe of
myocarditis wns experimentally produced by them in rats and mice.

In a series of 51 cases of diphtheria occurring consecutively among 6er- :
man Prisoners of War from North Africa, seven developed myocarditis. 'Only ;

^ four had cutaneous diphtheria and one of these had involvement of the myocar-
dium. All of the patients with cardiac signs had received sulfonamides; and"
all recovered. .

256

AMERICAN HEART JOURNAL

SUMMARY

A Study of this ease history with its pathologic findings leads to the con-
clusion that the myocardial changes were due to a combination of sulfonamides
and diphtheria toxin. The original lesion was not characteristic of wound
diphtheritis^® as it was covered by epithelium and was phlegmonous in character.
One must presiune that the Bacillus dipMlicriac was a secondary invader intro-
duced perhaps during the surgical intervention, as suggested by a personal
communication from Dr. C. V. Weller, who feels that such an atypical lesion
could be explained in this manner.

The cloudy swelling, simple necrosis, and granular fragmentation of the
myocardium is characteristic of diphtheritic myocarditis. In part, the inter-
stitial reaction, the round cell and polymoi'phonuclear infiltrations, and the
fibroblastic proliferation are subsidiary to these diphtheritic effects. It is cer-
tain, however, that additional, changes in land and degree were induced by
sulfonamide medication; the large pale mononuclear cells with eosinophilic
cytoplasm are considered to be representative. It is not, however, possible
to assess accurately the added influence of the lesion produced by the drag in
causing the fatal tei'mination.

The impression remains that the usual hazards of sulfonamide therapy
are increased when the heart is already damaged by diphtheria or other toxins.
In the course of such treatment it is necessary to evaluate, at frequent inter-
vals the state of the cardiovascular system as w'ell as to limit medication to
the quantity consistent with favorable results.

REFERENCES

1. Chin, K, _Y., and Huang, C. H.: Myocardial Necrosis in Diphtheria With a General

Review of the Lesions of tlic Myocardium in Diphtheria, Am. Heart .T. 22: 690,
1941.

2. Burkhardt, B. A., Eggleston, C., and Smith, L. W.: Electrocardiographic Changes and

Peripheral Nerve Palsies in Toxic Diphtheria, Am. J. M, Sc. 195: 301, 1938.

.1. French, A. J., and Weller, C. V.: Interstitial Myocarditis Following Clinical and Ex-
perimental Use of Sulfonamide Drugs, Am. J, Path. 18: 109, 1942.

4. Neubauer, C.: Diphtheritic Heart Disorders in Children, Brit. M. J. 2: 89, 1942.

5. Bramwell, C., and King, J. T.: Principles and Practices of Cardiology, London, 1942,

Oxford University Press, p. 476.

G. Saffron, M. H.: Cutaneous Diphtheria as klilitary Problem; Review of Literature With
Report of Case, Arch. Dermat. & Syph. 51: 337, 1945.

7. Rapport, H. M.: Desert Sores, Brit. M. J. 2: 9G. 1942.

8. Bull, U. S. Armj' M. Dept. 3: 21, 1944.

.1. Fleck, S,, Kellam, J, AV,, and Klippen, A, J,: Diphtheria Among German Prisoners
of War, Bull. U. S. Army M. Dept. 3: 80, 1944.

PAROXYSMAL VENTRICULAR TACHYCARDIA FOLLOWED BY
ELECTROCARDIOGRAPHIC SYNDROME ,

With a Report op a Case

Lieutenant Colonel Leslie B. Smith, M.C.

Army of the United States

S TRIKING electroeardiograiihic alterations' may persist for a long iieriod of
time after an attack of paroxysmal tachycardia in individuals who do not
liave evidence of structural heart disease. These changes are most prominent
following paroxysms of ventricular tachycardia and consist of depression of the
S-T segments, lowering or inversion of the T waves, and prolongation of the Q-T
inten'al. This phenomenon has not been generally recognized.

Graybiel and White^ (1934) were probably the fii'st to call attention to the
fact that there may be an inversion of T waves which graduall}^ return to normal
following paroxysmal tachycardia in individuals who do not have other evi-
dences of heart disease. Burak and ScherP (1933) reported that after an attack
of persistent paroxysmal tachycardia the electrocardiogram may for several
hours show negative T waves, lowered S-T segment, and alterations of the initial
deflections.

These electrocardiographic changes may be misinterpreted as indicative of
serious heart diseases, such as coronary occlusion, coronary thrombosis, myo-
cardial strain, cardiac damage caused bj" the tachycardia (anoxia, exhaustion),
toxic myocarditis, and pericarditis ; or the changes may be ascribed to quinidine
or digitalis intoxication.

The only review of this subject to date was that of Cossio, Vedoya, and
Bereon,sky,^ which appeared in the Argentine literature. They discussed their
findings after analyzing twenty-two cases. It is the purpose of this paper to
supplement their discussion, cite the three cases subsequently reported by Zim-
merman,^ and report an additional case.

case report

First Admission. — A 23-.vear-old man of Mexican and Indi.'in extraction was admitted
to the lio.spital on Oct. 6, 1944, complaining of a head cold and cough of four days’ duration.

He did not recall having had any illness in the past, even in childhood. Closer ques-
tioning revealed that five years previously he had an attack of "gas -on my stomach wliich
pushed up on ray heart and tended to shut off my wind. This spell lasted only a few hours
and stopped suddenly after the doctor gave me some white medicine. During the previous
three years he had had two similar attacks, each lasting ten minutes. ■ '

The present illness began four days' before , admission . -with a "head cold" and a
little sore throat and cough, which did not interfere with his participation in the rigorou.s
military training. The morning before, while .engaged in strenuous physical aephnty, he

Received for publication Axis:. 27, 1945.

, ■ ■ 257 ■ ■ ' . ‘

AMjiUICAM JIKAUT JOUKNAL

experienced a bunuug sensaliou ucrosn the front of his chest which wuH aggravated by deep
breatliing and coughing. He felt weak and .«hnky and noted ehdly sensationH, lieadaclie,

and malaise. . . , . -n

At the time of admission the patient was comfortable and did not appear 10 be 'vory ill.

The temperature was 101.20 JT., the apical heart- rate was approximately 190 .per minute,
•md the blood pressure was 90/70. There were numerous nsthmaloid rfiles heard in the bases
of both lungs, with' a few moist rales in the loft base. There were no other abnormal physical find-
ings. Tlic leucocyte count was 15,780 per cubic millimeter with 75 per cent polymorpho-
nuclears cells. An x-ray film of the chest revealed a moderafe-.si/.cd area of pneumonia in
the medial portion of the viglit lower lobe. An electrwtardiogram (I'ig 1, /I) slioacd a
ventricular tachycardia with a ventricular rate of 159 and an auricular rate of SO per minute.
The duration of the QTttS complex an.- 0.10 to 0.11 second; nil of the limb lead.« showed deep
and slurred S waves. Tlic only 'major deflection in CF^ was upright.

, The temperature was riormal four honr.s after admission and wn.s not significantly
elevated during the remainder of the illnc.'-s.

Kig. 1. — Serial electrocauliograms made during llnst hospital mlmlsslon. See text for lic.-^crlpllon.

. ’ Repeated attempts to stop the tachycardia by ocular pressure nnd 'massage of the
carotid sinuses wete unsuccessful. A test dose of 2 grains of quinidino sulfate was given.
He was then given -1 grain.s of quinidiuc sulfate every three hours for four doses.

The second day the tachycardia per.^isted and the dose of qninidinc was incrcjised to
6 grains every two hours for an additional five doses. Then 10 c.c. of calcium guleatc wore
given intravenously without afTecthig the heart rate. The electrocardiogram was essentially
unchanged. Tj-po 32 pneumococci were found in the sputum. Asthmatpid rales were present
in the chest, but there were no other abnormal physical findings. These findings remained

unchanged during the tlurd day. Because of the pneumonitis and the tachycardia the patient
was placed in an oxygen tent.

Durmg the fourth day he complained of smothering sensations and inability to get his
■ breath. . Ho became less dyspneic in an oxygen tent. Tljcre was moderate distention of the
nec veins. ar y in the day the left lobe of the liver was found to bo enlarged and
tender, and several hours later the right lobe had become palpable and tender. The pul.'=c

SMITH: l^UiOXYSaiAH.AT^NTItlCULAB „TACHYCAKD1A ■

rate remained apjtroximately IGO per minute and- the blood, pressure was S6/70. . Quinidine
therapy was again instituted in doses of '6 gra,ins every hour for four doses, theii 6 grains :
every two hours. After the third dose of quinidine, % grain of morpliine sulfate, was given. .. ,

Tlxis medication was supplemented with 4 drams of ipecac,, which induced vomiting -vyithout
altering the .heart rate. Electrocardiograms (Fig. B) made this day showed a ventricular
rate of 1G2 per minute, an auricular rate of 80 per ‘minute, a QRS interval of 0.12^ second, :
deep and slurred S waves in the limb leads, and inversion of the T waves in Leads II, ‘
in, and IV. ' '

The next morning the jjulse rate was 154 per minute, and tliirty minutes later the rate
was 84 per minute. >Seventy-eiglit grains of quinidine .sulfate were given during tlie twenty;. .
four-hour period preceding the change to normal rhythm. An electrocardiogram (Fig. 1, G) .•
recorded ajjproximately thirty minutes afteV cessation of the tacliycardia showed a QES
interval of 0.08 second, marked depression of tlie S-T segm'ents in Leads II and ni,
wide and deeply inverted T waves in the limb and precordial leads, and a Q-T interval .
of 0.558 second. Another electrocardiogram taken three hours later -was essentially the
same. During the first day of normal rhj’-thm, the patient was no longer dj'spneic and there' . '
was a marked clearing of the rales in both lungs. Quinidine medication was discontinued
for six hours, then IV 2 grains were given every four hours fpr seven doses.

■ p. DI'C 4 /? -

^5;

m

.tK

•rVJ

pM'm

' r ..H •_ B ...

Fig. 2. — Se,rlal electrocardiograms made during ftr.st hospital admission. See text for description^

The next day he complained of a mild headache, right earache, and deafness , in the
right ear. The liver was no longer enlarged or tender. The temperature was normal and
the leucocyte count was 10,0,00 per cubic centimeter \vith 80 per cent polymorphonuclear cells.
There was some injection of the right eardrum, and sulfadiazine was given in 1 ., Gmi doses
every four hours for nine days. A diagnosis of nonsuppurative otitis . media was • made.
These symptoms subsided rapidly, and the temperature remained normal.

■ On the eleventh day a roentgenogram showed almost comlplete clearing , of the pneumonic
process. The patient continued to be free of .symptoms, and the physical examination revealed
no abnormal findings. Because of our uncertainty as. to the significance 6f the electrocardio-
graphic change.s, he was kept in. bed until tlie twenty-first day, when graduated exercises'
werd begun'. At this time the electrocardiogram (Fig. 2, B) showed • diphasic T T and T
and deep inversion of T^. - . , ' ' - , - . Z*

260

AMERICAN HEAET JOURNAL

Tlio convalescence continued to be uuoventfiil, and iihysical findings wore normal
except for persistence of coarse rales in the baso of the right lung. Frequent examination
failed to elicit a friction rub or cardiac niurinur.s. A teleroentgenogram on the ninetcentli
day and a fluoroscopic examination on the sixty-fifth day were normal. He was transferred to
the rehabilitation facility on the seventy-first day, where ho remained asymptomatic. One
hundred five days after Admission, electrocardiograms made immediately after one and
one-half minutes of stationary running, and thereafter at intervals of five, ten, fifteen, and
twenty minutes, showed no changes in any portion of the complexes.

Second Admission . — ^Following the first admission lie did duty as a cook, worlting
twenty-four-hour shifts witli twenty-four hours oif duty between tlie shift.s. lie stated that
he had felt well, and that the work did not fatigue him.

Fifteen hours prior to this admission, following the consumption of a "large amount
of beer and a few whiskies, " ho noted a sudden onset of a buniing sen.sation in the region
of the sternum, a slight choking sensation at the base of bis neck, and a pulse rate which
he said was too fast to count. Ho had slept poorly that night, but reported for duty at
4:30 A.M. In about six hours be became too weak to continue bis duties and was sent to
the hospital.

Pig. 3. — Serial electrocarilioEram.s made durinK second hospital admission. The tracing's are

described In the text.

At the time of admission he complained only of a mild burning sem<ation, located
under the sternum, and a slight choking seilsation. Examination revealed an irregular pulse
with a rate of 170 per minute, with a tic-tac rhj-thm heard at the apex. The blood pressure
was 94/80. There were no other abnormal findings. An electrocardiogram (Fig. o, A)
revealed a ventricular tachycardia with a ventricular rale of 150 per minute and an
auricular rate of 98 per minute. The complexes were virtually the same as those during the
first attack, and showed the deep and slurred S waves in all limb leads. Ho was aware that
his heart rate had returned to normal following six hours of quinidine medication, during
Tv^ch time he received 19% grains. An electrocardiogram (Fig. 3, B) taken two hours
after the return of normal rhytlim showed a diphasic T^ inverted T., T„ and T„ slight
elevation of S-T, and S-T„ and a depression of S-Tj, and S-T^.

, The patient felt perfectly well during this stay in the hospital. He urns kept at
led rest for four day.s. Tlicre were no evidences of heart disease or of other abnormal find-

SMITH: PAROXYSMAL VENTRICULAR TACHYCARDIA . .. ~ 261

ings. The blood counts, urinalysis, and sedimentation rates were nonnal. There -was a-
gradual evolution of the electrocardiogram (Pig. 3 ) . to normal on the fifteenth day, = and .
the patient was returned to limited duty. . ■ ,

Third Admission . — He had been well since the last admission except that on "two
occasions, two months and one month before, he had noted periods of burning in the left,
side of the chest, "vnth irregular heart action lasting one and one-half to two hours. ■ .

At 11:00 A.M. on the day before admission he noted a burning sensation, Avhich he
located at the level of the xiphoid process, and was aware of an irregular and fast heart
action. Tliere were no unusual circumstances preceding this attack. At the time of admission
his comi)laints wore minimal, and there were no abnormal physical findings except the tachy- '
cardia. The ventricular rate was KiO and the blood pressure was 90/70. The leucocyte ,
count, urinalysis, and blood sedimentation rates were normal. An electrocardiogram (Pig.'
4, A) showed ventricular tachycardia with a ventricular rate of 160 per minute and an
auricular rate of 80 per minute. This attack terminated spontaneously after a total duration

Fig. 4. — Serial electi’ocardiograms made during the third hospital admission. The tracings are,
described in the text. There is a reversal of polarity in Lead HI of tracing A.

of twenty-four hours. An electrocardiogram (Pig 4, B) taken one hour after the return of
normal rhythm showed slight elevation of S-T, and S-T,, depression of S-T,, with inversion
of T, and Tj. This electrocardiogram resembles that of a posterior infarction. The next day
(Fig 4, C) the elevation of S-T, and S-T, was not as prominent, and the T-wave inversions
were deeper. Two days later the T-wave inversions were less prominent; on the eighth
day the T waves were all upright, and on the thirteentli day the voltage of the T -waves
was normal. The temperature, the leucocyte count, and the blood sedimentation rate during-
this admission remained normal, and the patient was ' discharged to limited duty on the:
fourteen til day. ' ‘ ,

Ten days after the third admission he had an attack which lasted two hours. Electrb-
cardio^ams taken the following day and three, days later were normal. A teleroentgenogram '
was*: normal. . ' ' , . • ' , ;

262

AMERICAN HKAHT JOURNAL

Cose Suwoiovy. — 23-yc{U’-old iiiun wns uclniiltcci to the hospitul Ihiei
times during attacks of ventricular tachycardia. Tlie past history disclosed
that during the previous five years he had symptoms wliich in view of the present
findings were interpreted to represent three short attacks of paroxysmal tachy-
cardia. The first attack observed by us lasted four days. This attack was asso-
ciated with a '‘cold" and pneumonitis, Avhieh was diagnosed as mild atypical
pneumonia, etiology undetermined. During the fourth day of this attack there
was definite evidence of heart failui'c which cleared promptly following the
cessation of the paroxysm. Seventy-eight grains of (piinidine sulfate were a<l-
ministered during the twenty-four-liour period preceding the termination of the
ninety -six-hour paroxysm. There were no evidences of struetural heart disease.

The posttachyeardial electrocardiographic manifestations were of unusual
interest. After the cessation of the attack the T waves were deeply inverted in
all leads, with depression of the S-T segment in Leads II and III and prolonga-
tion of the Q-T interval. At first these ehangas were thought possibly to repre-
sent quinidine intoxication; however, these abnormalities persisted long aftei-
the action of quinidine bad subsided. Serial electrocardiograms (Figs. I and 2;
showed persistence of the abnormal change.s, with a gradual return to nonnai
in fifty-seven daj’S. The patient felt well durinu tlie jieriod of observation, exeejit
during the fourth day when heart failure wav ^n-esent and during the days of
catarrhal otitis media. At no time after the eessation of the tachycardia were
there any abnormal cardiac finding.s, and the laboratory finding.s Avere nonnai.
Although the clinical findings did not substantiate a diagnosis of .struetural heart
disease, various diagnostic impressions were ofi'erod by obsorvei's and reviewers.
These included myocardial infarction or decrease in circulation due to obstruc-
tion in a possible anomalous coronary system'’ and toxic change.s in the myo-
cardium secondary to acute infection.® The author, at first, was of the opinion
that the electrocardiographic manifestations, although atypical. Avere due to a
pericarditis associated AAuth the pneumonic process in the left loAver lobe. A
definite final diagnosis Avas not established, but it Avas decided at the time of
discharge that struetural heart disease Avas not present.

The second ]iaroxysm of tachycardia, which lasted twenty-one hours, AA-as
possibly precipitated by alcoholic excess. The posttachyeardial changes Avere
not as marked as during the first attack and returned to normal more rapidly
(fifteen days). The patient had had Iaa’o short paroxysms betAveen the second
and third admission. The third obsen-ed attack of ventricular tachycardia
lasted twenty-six hours before it terminated, spontaneously. The electrocardio-
graphic changes this time did not include depre.ssion of S-Tn and S-Tn or neea-
tivity of Ti, and there Avas a return to normal in twelve days.

It is thought that this series of electrocardiograms are representative of a
postparoxysmal ventricular tachycardial sjmdrome. The sequence of the electro-
cardiographic changes are in keeping Avith the postulates of Cossio, Vedoya, and
Bereonslqr.® Figs. 1 and 2 shoAv a ventricular tachycardia with deep and slurred
S waves in the limb leads. This Avould indicate an automatic ventricular focus
located some place in the lateral portion of the left ventricle giA'ing rise to a past-

SiMITH ; PiVROXi'SlMAL YENTRICULAR TACHYCARMA

tac%cardial electrocardiogram of predominant T 3 . .(T 3 and T 2 ) tj^ie with sonic
negativity of Tj. Fig. 2 is of the same T 3 • t^^)e, but has . less prominent Ti
changes, which may indicate that the focus was more posterior, The T waves
in Lead I are positive in the posttachyeardial electrocardiograms (Fig' 4) taken
after the third attack. These electrocardiograms may be interpreted as indicat ; .
ing that the foens was more' posterior than it was during tlie previous two
attacks. ' '

The difference in the degree of the changes in the three series of electro-
cardiograms is probably not directly related to the duration of the paroxj'shl.
The duration of the third paroxj’^sm showing no Ti or T 4 changes was longer, .
twenty-six hours, than that of the second paroxysm, twenty-one hours, in which .
Ti was definitely negative.

DISCUSSION '

The electrocardiographic syndrome following paroxysmal tachycardia con-
sists of changes in (1) tlic T waves, (2) the S-T segments, and (3) the duration
of the Q-T interval. The most characteristic T waves are those which are deeply .
inverted, -with a broad base and almost equal limbs. However, these may vary
in degree from simple reduction in voltage to varying depths of inversion of the
T waves. These changes may be present in all three limb leads, Lead I or .
Leads I and II (T^ type), or Lead III or Leads II and III (T^ type). Negative
T waves in all three limb leads was a predominent finding in .two of the twenty- . '
two cases previously reviewed,® and in the author’s case (Pig. 1 ).

The S-T segments are usually depressed in one or more leads (Fig. 1, B).
These S-T depresisions are most prominent in the same leads whicli have the
most marked T-wave inversions. Another feature is that the T-wave changes
usually persist for a long period : six to sixty daj’-s.^’ ‘ A slight reciprocal eleva-
tion of the S-T segment in the oppo.site limb lead may occasionally be present: ,
(Pig. 4, B). Prolongation of the Q-T interval is common.

Although paroxysmal tachycardias of auricular origin occur more than '
ten times,®’ ® as frequently as those of ventricular origin, only two cases of pure ,
auricular paroxysmal tachycardia have been reported in which there were some
alterations in the posttachyeardial electrocardiograms. In one of these two
cases, that reported by Zimmerman,^ the T-wave changes were minimal ; there .
were no depressions in the S-T segment-s, and the abnonnality la.sted less than :
two days. Two of the other six reported cases of supraventricular origin hiid
aberrant ventricular complexes, and the other four cases showed the Wolf- -
Parkinson- White sjmdrome. There are now nineteen cases on record in which .;
this syndrome followed paroxysmal ventricular tachycardia. These electro- v '
cardiographic manifestations seem to occur so infrequently following auricular
paroxysmal tachycardia, and the magnitude of the changes are so much less that i
it seems .iustifiable to state that. these alterations of , the riectrocardiogram con-, i
stitute a characteristic electrocardiographic syndrome which may be present , •
following paroxysmal ventricular tachycardia. : '

264

amemcan heaut joubnae

At tlio present time it cannot be determined bow frequently this syndrome
follows ventricular tachycardia. However, there are a number of publi.slied
electrocardiograms made following attacles of ventricular tachycardia which
• show otherwise unexplained changes similar to those under discussion."-^®

That this syndrome is more related to the ventricular structures than to the
supraventricular structures is emphasized by Ihe correlation between the con-
tour of the electrocardiogram during the attack of paroxysmal ventricular tachy-
cardia and the pattern which follows the tachycardia. From an analysis of the
precordial leads in one of their cases, Cossio, Vedoya, and Berconsky® thought
that the sequence of disappearance of the negative T waves Avei'o exiu'cssions of
a localized myocardial disorder. They found that in all of the six cases with
left axis deviation during ventricular tachycardia and two cases of supra-
■\-entrieular tachycardia v-ith aberrant ventricular complex there was a Ts type
(negative T 3 or negative To and Ta) of post tachycardia electrocardiogram. The
two additional cases of ventricular tachycardia reported by Zimmerman'* showed
left axis deviation during the paroxy.sm and the Ta type of pattern following
the attaelcs. All three eases of ventricular tachycai’dia with right axis deviation
during the attack had T^ types (negative T, or Tj and T,) following the paroxysm.

Pour of the collected cases® and the author’s case (Figs. 1,A, H, A, and 4, A)
showed wide notched Si waves with deep slurred So and Sa waves and the Ta
type of posltachyeardial electrocardiogram. Four of these casc.s .showed some
negativity of Ti. The autlior's case (Pig. 1, 0), besides deep inversions, of To
and Ts, showed a deep inversion of Ti two hours after termination of the four-
day paroxysm. Pig. 3, B, shows a smaller negativity of Ti after the attack of
twenty-one hours’ duration, and a positive Ti (Fig. 4, B) after an attack of
twenty-six hours’ duration. These cases represent combined T] and Ta types,
excepting the tracing shown in Pig. 4, B. Cossio and his co-workers® postulated
that in this group the ectopic foeus is situated on the posterior or posterior
lateral portion of the left ventricle rather than on the anterior face, and that
the Ta type should be expected with a negative Ti which vdll be of more promi-
nence the nearer the focus is to the anterior surface. If this hypothesis is true,
the electrocardiograms recorded in the author’s case represent different active
foci during each of the attacks; Fig. 1 , G, shows the most anteriorly located
foeus and Pig. 4, B, shows a more posteriorly located focus. In all the sixteen
cases of ventricular tachycardia studied, the posttachycardial electrocardio-
, graphic pattern could be determined by the QRS complexes present during the
attack.

These findings suppoif the contention of Cossio, Vedoya, and Bereonslej'®
that from the contours of the electrocai'diogram during the attack of paroxysmal
tachycardia, especially in tlie ventricular type, the automatic ectopic foeus which
originates pe tach5^eardia can be located and the type of posttachycardial
electrocardiographic configuration can be predicted.

Although the validity of this concept may be questionable, the frequency
^h which the posttachycardial pattern can be predicted by the contour of the
during the paroxysm is probably more than a coincidence.

, SMITH: PAROXYSMAL VEXTRICULAR TACHY’CARDLV 265

' Geiger^® first called attention to the occurrence of a prolongatioii of- the Q-T
Interval following paroxysmal tachycardia. In his case, the Basett index (K) ..
was ,0,509 and 0.535 (normal, 0.392). Cossio and his associates found that in
nine cases K varied from 0.45 to 0.60 with an average of 0.516. In the autlior/s _
case the average K during the first day following a four-day paroxysm was
0.558; however, K equaled only 0.387 following an attack of twenty-four hours'
duration.

, . The mechanism of production of the iiosttachycardial pattern is not Impwn;
Various authors have offered theoretical explanations, such as cardiac in-
sufficiency^^ ; fatigue and exhaustion of the myocardium resulting from the pro-
longed attacks of tachycardia^^ ; overload of the myocardium connected witli the
duration of the attack^^; myocardial ischemia associated with a sharply
diminished cardiac output during the many hours of high ventricular rate, ’
producing a reversible injury^® ; modification of a chemical or other nature
of the myocardium"; cardiac damage caused by the ..tachycardia (anoxia, ex-
haustion)^®; and. occult coronary sclerosis. These theories all postulate some
disproportion between the blood supply and the work of the heart or some type
of structural damage. That these conditions exist as the cause of the post-
tachycardial electrocardiographic alterations is liardB’- tenable for the folio-wing
reasons: the attacks of auricular tachycardia may persist for weeks without
producing these electrocardiographic changes; the syndrome almost always fol-
lows paroxysmal ventricular tach 3 ’-cardia ; the duration of the ventricular tachy-
cardia is not directlj’- related to the posttachy cardial electrocardiographic
changes, as they may occur after attacks as brief as three hours^'*; the electro-
cardiographic changes may persist for long periods (two months) unassociated
■with impaired cardiac function; and the syndrome may be repeatedly sho-wn in
the same patient -without evidence of structural heart disease.

Two eases which came to autopsy® did not have demonstrable heart disease,
and only three®’ ^ of the twenty-six eases now cited were thought to have clinical
heart disease; hence, it does not seem likely that organic heart disease plays a
significant role in the production of the posttachycardial syndrome.

, . The most plausible explanation® is that the localized automatic focus, which

is responsible for the paroxysmal tachj’^cardia, retains gradually diminishing
activity which causes the posttachycardial electrocardiographic changes.

CONCLUSIONS

• 1. A 'case is reported of a patient without structural heart disease whose
electrocardiograms are examples of a postparoxj’-smal ventricular electro-
cardiographic syndrome.

2. The postparoxysmal ventricular s.yndrome is characterized by inversion .

of the T waves in one or more leads, with depression of the S-T segments in the
leads where the T-wave inversions are the most prominent, and by prolongation
of the Q-T interval. . . ^

3. The 'type of the postventricular tachj^cardial manifestations can be
predicted from the QRS components ^vhich are present 'during the paroxysm of

266

AMERICAN HEART JOURNAL

ventricular taeliyeardia. When left axis deviation is present during the
paroxysm, it may be assumed that an automatic focus is active in. the light
ventricle and predicted that the posttacliycardial pattern will be a T3 type
(negative T3 or negative Ta and T3'). When right axis deviation is present dur-
ing the tachycardia, the focus is probably in the left ventricle and the post-
tachycardial electrocardiograms will be the Ti tj-Tie (negative Ti and Ta). In
those eases where slurred and deep S waves are prominent during the paroxysm,
it is assumed that the automatic focus is' in the left lateral portion of the heart
and that a combination of Ti and T3 types will follow, with the negatmty of
Tj most marked when the focus is more anteriorly 'located.

4 . As postulated by Cossio, Vedoya, and Berconslc5%® it is thought that the
automatic focus which is responsible for the paroxysmal ventricular tachy-
cardia retains some type of activity after the cessation of the tachycardia, in-
fluencing the electrical phenomenon to produce the abnormalities of the T
waves, S-T segments, and the Q-T intervals.

5 , This sjTidrome is not indicative of serious heart disease, fon which it
maj'^ be mistaken.

REFERENCES

1. Graybiel, A., and White, P. D.: Inveision of the T Wave in Lead I or II of the

Electrocardiogram in Young Individuals With Neurocirulatorj*' Asthenia, With
Thyrotoxicosis, in Relation to Certain Infection'^, and FoTlovring Paroxysmal Tachy-
cardia, Axt. Hermit J. 10; 345, 1034.

2. Burak, M., and Scherf, D.: Quoted from Seherf, D., and Boyd, L. ,T.: Clinical Electro-

cardiography, ed. 2, St. Louis, 1941, The C. V. Mosby Co., p. 138.

3. Cossio, P., Vedoya, R,, and Berconsky, I.: Modifications of the Electrocardiogram FoRou-

ing Certain Attacks of Paroxysmal Tachycardia, Rev. argent, de wirdiol, 'll: 164,
1944.

4. Zimmerman, S. L.: Transient T Wave Imersion Following Paroxysmal Tachvimrdia, ,7.

Lab. & Clin. Med. 29: 598, 1944.

0 , Herrmann, G. : Personal communications, October, 1944, and January, 1945.

0. Barnes, A. E.: Personal communications, Deeembei, 1944.

7. Campbell, M. : Inversion of T Waves After Long Paroxysms of Tacbveardia, Brit. Heart

J. 4; 49, 1942.

8. Palmer, R. S., and White, P. D.: Paroxysmal Ventricular Tachycardia With Rhythmic

Alternation in Direction of the Ventricular Complexes, Ail. Heart ,T. 3: 454. 1928.

9. Eiseman, ,T. E. F., and Linenthal, H.: Paroxvsmal Ventricular Tachycardia. Ait. Heart

J. 22: 219, 1941.

10. Williams, C., and Ellis, L, B.: Ventricular Tachycardia, Arch. Tnt. Med. 71: 137. 1943.

11. Campbell, M., and Elliott, G. A.; Paroxysmal Tachycardia; Etiology and Prognosis of

One Hundred Cases, Brit. M, J. 1: 123, 1939.

Wliite, P. D.: Paroxysmal Tachycardia, Brit. Heart J, 5; 33, 1943.

13. Duhhs, A. W., and Parmet, D. H.: Ventricular Tachycardia Stopped on the Twenty-First

by Giving Quinidine Sulfate Intravenously, Ail. Heart J. 24: 272, 1942.'

14. Currie, G. M.: Transient Inverted T AVaves After Paroxi'smal Taclivcardia, Brit. Heart

J. 4: 149, 1942.

15. Geigei , A. _ .T. : Eleeti ocardiogr,ams Simulating Those of Coronary Thrombosis After

Paroxysmal Tachycardia, Ail. Heart J. 26: 555, 1943.
o. bcherf, D^ Alterations in the Form of the T Waves With Changes in Heart Rato,
Am. Heart J. 28: 332, 1944.

Abstracts and Reviews

Selected Abstracts

Bussek, H, I., Southworth, J. L., and Zohman, B. L.; Selection of the Hypertensive Patient

for Sympathectomy. J. A. M, A. 130: 927 (April 6) 1040.

In view of the increasing frequency with which sympathectomy is being performef]
in the treatment of ]i 3 ’pcr tension, it ])ecomes of growing im])orfance to develop an accurate
liiean.s b 3 ’' which favorable cases ma.v be selected. Sodium nitrite, sodium arnytal, and coM
pressor tests, while still widoU' used, have not proved to be entirelj’ sati.sfactorj'. Wliile
high .spinal ane.sthesia appears to yield some information in the determination of favorable
patients for operation, it introduces various factors which give misleading results. Thus
the loss of muscle tone and complete motor pnral.v.sis observed in the lower part of the
body in spinal anesthesia maj', of themselves, matorialh' alTect the height of the blood
pressure through tlic medium of venous stasis, diminislied venous return to the heart, and
fall in cardiac output. The heraodr’iiamic response to this procedure does not .seem com-
parable to that following surgical sj’inpathectomj'.

The use of caudal aucsthesia i.s suggested ns a means of selecting hypertensive pa-
lientfi for surger.v. The following are some of the advantage.s of continuous caudal anes-
thesia: (1) muscle tone and motor power of the lower e.vtremitios are little alTocted; (2)
respiration is essentially unchanged; and (3) the height of anesthesia is easily and safely
raised to the desired level bv repeated small injections. Tliese authors maintain that In-
gradual and progressive block of sympathetic nerve segments from below upvrard, a clear
concept may be obtained concerning the degree of neurogenic influence and extent of sur-
gery huUcrtled in the given case. They give 5i dose which sufnec-s to cause a gradual rise
in the level of skin anesthesia in the sixth thoracic .segment. By this method they were
able to lower the blood pressure of hypertensive.^ to normal in 42 of CO i)riticnis. By levels
of anesthesia varjnng from the tenth to the. fourth thoracic segment, they were able to
accurately predict the outcome of surgical sympathectomy in .11 of 12 patient.®, whereas
other tests were found unreliable when omplo^-ed for this purimse. Bki.t.ct,

f

Idan, C.; Caxdlo-Esopliageal Auscultation, Arch. d. mal. du co-ur. 38: 221 (Sept.-Oct.) 194n.

The author's technique of c.sophageal nuseultation is to pass a Fauclicr gastric lavage
tube, or preferably an Einhorn tube, into the c.sophagus and to .attach the ear piece.s of a
binaural stethoscope to its outer end. Cardiac auscultation was performed b.v tlu.s mean;-
in a series of twenty-six patients. In three patients, auscultation -was imsatisfactdry be-
cause of nausea. It is reported that valvular murmurs of all t>-pes us w'cdl as the heart
sounds can be clearly heard when the breath is Iicld during inspiration and expiration. The
murmur which i-s best heard is that of mitral insufilciency because it pre.sumhbly arises
from the left auricle which is in close approximation to the csophagu?. . ,

Attention is. called to the value of esophageal ranscnltatioa in the diagnosi.s of laitnal
in.sufliciencj*. The author .states that if no murmur is audible when the end of the tube
is at a level 20 to 40 cm. below the dental arch, the conclusion i.« warranted th.at there is
no insuflicicncy of the mitral valve, . .

An auricular presyslolic sound .was very rarely audible b\- esophageal .auscultation
in normal stibjccts. - This observation supjujrts. tb.e view that the presystolic auricuisr sound

268

AMEUICAN IIE.VRT JOURNAL

which appears on phonocardiograms is uctuallj' exceptional as an audible pbenoinenon in
normal- subjects in contrast to the frequency with which the physiologic third sound is
heard. ■ Latlace.

Cotlove, E., and Vorzimer, J. J.: Serial Prothrombin Estimations in Cardiac Patients;

Diagnostic and Therapeutic Indications, Esc of Dicumarol. Ann. Tn(. >ted. 24: G48

(April) 1946.

Prothrombin activity was studied in the following subjects: nineteon patients with
cardiac disease of heterogeneous typos without einboli.sm, thirteen patients with variou.-
types of cardiac disease and ns.sociated embolism, five noncardinc patients with thrombo-
phlebitis and pulmonary einboli.sm, and three noncardiac patient.s with thrombophlcbiti.s
without emoblism. The “controls” were thirty -five healthy hospital workers or patient.-
with “various diseases” whose nutritional status and physical condition were good. In
the patients studied, serial prothrombin c.«fiinations were made from one to .six time.- a
week, and most cases wore followed for two weeks or more. None of the piitient.s received
salicylates, and vitamin K and dlfUina.T' wore not given exeejit in a few ease- speeiftcally
studied. The readings included wl.oh pui'-'nin prothrombin time and the 12.5 per eeht
diluted xilasnia prothrombin time, as recommended by Pimpiro and others. The xiurjiosc of
the dilution was to render inonVetive the naturally occurring anticongulnnt.s of the blood.
For this reason, the authors place greater stress on Iho diluted plasma i>rothrombin time
in evaluating their data. In the normal controls, the figure.- obtained by these author.s
were 17.8 ±2 seconds (whole idasma) and 45.2 ±5 seconds (diluted plasma). Of the eight
cardiac cases with pulmonary embolism and infarction, four showed no deviation from
normal, three showed an insignificant deviation, and only one .showed any abnormal shorten-
ing of dilute pla.sma prothrombin time. In the two case.- with myocardial infarction “with
mural ventricxilar thrombosis and peripheral embolism, and in the tliree case,' of chronic
rheumatic heart disease with auricular thrombosis and associated embolism, increased
prothrombin acth-ily was not present. Of the five noncardiac patients with throrabo-
' phlebitis and pulmonary embolism, all showed normal whole jilasma prothrombin times.

but four showed accelerated diluted plasma prothrombiu time. On the contrary*, of the
I- cases of thrombophlebitis without embolism, only one manifested a shortened diluted
plasma prothrombin time. Of the 19 cardiac patients without frank embolism (which
included five patients with acute coronary occlusion and five with angina xiectoris) an nVi-
normal acceleration of the diluted plasma prothrombin time wa.s encountered only Uiree
times, but in two of these instances, imlmonary infarction could not be entirely excluded.
It is significant that digitalization, bed rest, or congestive failure did not significantly
modify the prothrombin times. Six cardiac patients were given dicumarol therapeutically
after embolism appeared. In all these, a significant xirolongation of prothrombin time was
achieved with less than the usually recommended amounts. The authors, therefore, suggest
a tentative dosage schedule for cardiac patients. It is their opinion that the ideal indica-
tion for the use of this drug in cardiac disease is the presence of phlebothrombo.-L- or
thrombophlebitis. They also caution that dicumarol should never be used unless there are
facilities for accurate daily estimations of prothrombin. Included in the pajier is a lengthy
and complete discussion of the tcehnical considerations involved in the xierfornmnco of
tests for prothrombin time. ’Wentiko.';

Oharr, E., and Swenson, P. G.; Clubbed Pingers. Am, J. Roentgenol. 55: 325 (hlarehl’

1946. • '

The superficial arterial vessels were studied by these authors in six early cases of
clubbed fingers to further aid in understanding the pathogenesis of this condition. No
bone changes were demonstrable by the roentgenogram. Injections of diodrast into the
ra lal arteries in several patients were first tried but were technically un.satisfactory. The

SELECTED ABSTRACTS

. 269 .

methods finally used were infrared photography in the living, and iiijec'tion of a suspen- .
sion of barium sulfate post mortem. Three of these patients had died of advanced
pulmonary tuberculosis. The clinical findings in the remaining three living patients ■were
advanced broncJiiectasis, pulmonarj' necrosis following pneumonia, and pulmonary tuber-
culosis . associated with congenital stenosis of the pulmonary artery. None, of the six
cases had evidence of congestive heart failure. They found an increase in the number
of blood vessels, with wider lumina, about the tips of the fingers. '

The authors state that while their observations substantiated the anatomic studies
pre\’iously described, the results of their study of blood flow in patients with clubbed
fingers were at some variance with the reports of others. The prevailing opinion seems
to be that the bone changes, the hypertrophy, and the hyperplasia of the soft tissues
present in clubbing result largely , from the increased nutrition brought about by increased
peripheral blood flow. Mekanze.

Parker, K. L., Dry, T. J., Willius, F. A., and Gage, R. P.: Life Expectancy in Angina

Pectoris. J. A. M. A. 131: 95 (May 11) 1946.

Recent follow-up studies of patients with angina pectoris have shown a favorable
lengthening of the average survival period. These authors made follow-up studies on
3,440 cases of angina pectoris. The average age of the patient at the time of onset'
was 57.1 years. The majority of the patients had sufliered with angina pectoris for a
period of two years or less prior to the examination (74.3 per cent). In 2.8 per cent,

symptoms of angina pectoris had been present for ten years or more prior to the time

of examination. The ratio of men to women was 4.3:1. The highest mortality date was
observed in the first year following examination. During this year, 18 per cent of the
patients succumbed. Following the first year, the mortality remained nearly constant,
averaging approximately 10 per cent among those who had survived the disease for three
years. The survival rate was higher for women than for men. Associated conditions, such ,
as cardiac hypertrophy, well-defined hypertension, previous cardiac infarction, congestive
heart failure, and significant ’electrocardiographic abnormalities were clearly related to
a higher mortality rate and lower survival rate. . Eellet.

Gregg, D. E.: The Coronary Circulation. Physiol. Rev. 26; 28 (Jan.) 1946.

This article consists of a review of the coronary circulation particularly from the

standpoint of physiology and pharmacology. There is a brief resume of the anatomy and
the experimental approaches to the study of the coronary circulation. The various methods
of measuring coronary blood flow are discussed and some points of possible error and
inadequacy, of these measurements as applied to the problem in man are emphasized.
The author brings’ out the fact that the reported observations dealing Avith the coronary
flow, its minute volume, distribution, and ultimate drainage, its response to drugs, the
effects of nervous and humoral influences, and the effects of changes in aortic pressure,
peripheral resistance, cardiac output, cardiac work, and metabolism are often made upon
preparations that are abnormal and under conditions that are artificial.. All too often
results obtained with a decidedly abnormal preparation ultimately come to be regarded
as events which can and do occur in the normal animal or man. Various concepts con-
cerning the coronary circulation haAm frequently been revised, as new and improved
instruments and preparations have been developed. Much of Avhat has been reported '
in the past should be discarded as more accurate methods for making the same physiologic
studies become available. He concludes that until better instruments and methods are
devised and used in conjunction Avith preparations which are. capable of normal physiologic
. responses, our knowledge concerning the normal and abnormal functioning of the coronary
circulation will be necessarily limited as Well as unavoidably inexact. .-d

AMKRICAK heart JOUKN'Af.

270

Norpoth, Ii., and Vagades, K.: Dlsturl)anco8 of the PacomaUor and of Condiictlon In
Addison’s Disease. Ztschr. f. KreislaufVorpcli. 36: G73 (Dec.) 1913.

The literature reporting electrocardiographic findings in Addisoii's disease is re-
viewed. Among the abnormalities reported have been varying degrees of A-V heart bloch,
prolongation of the Q-T interval, low voltage, T-wavo inversion, and, sometimes, RS-T
segment depression. One case is added by the nnthor,«. 'Iho patient nas a 31-ycar-old
man, with a minor grade of A-V heart block in which the 1^*R interval shortened, to top-
normal duration with exercise. During a sub.seqncnt crisis sinus arrhythmia, brady-
cardia, extrasystoles, and periods of ' sinonnrlenlar heart bhx’k or A*V nodal rhj'thrn
appeared. All of these ubnorniaUties disappeared following the administration of cortical
hormone. ' Sayex.

von Dirlngsiiol'en, H., Sane, H., and Strnad, W,: Study of the Roentgen Density of the
Lungs in Humans as a Measure of the Pulmonary Blood Plow. 2t.schr. f. Kreis-
laufCorsch. 35; 402 (Aug.) 1943,

The authors believe that variations in the roentgen density of the peripheral lung
Held in excess of those occurring with normal respirntion should provide an index of the
pulmonary blood content. Their method was to moiisuvc the ilhiinination of a portion
of the right lung by a pliotoclecfnc cell in front of a lluori).‘»(‘op!c .'u'roen. P.y the use
of a tilt table, the variation in lung rlen.sity of normal .siibject.s in variou.s po.'.itions could
be studied. The roent’gou density of the lung decrca.sed .•jignifietuitly with .shifts from the
erect to the recumbent position. The head-down ]iositioii increased the density, and light
oxerei.se Imd a similar efTcct. Changes in the degree of density under these conditions
werc'sevcral times greater than those resulting from quiet resjiiratiou, When the breath
was held against a pressure of about one atmosphere, decrease in density wn.s ob.served;
a further decrease in density was ol)scrved to follow shifts from the vertical to the
horizontal position. Administration of low-oxygon mixtures and of adrenalin or hi.stamine
produced no significant ofiTocts. The authors' concluded that, contrary to c.xpectations,
the blood content of the lungs decrease.s in recumbency in spite of incrcn‘<ed venous
return. The mechanism is obscure. The possibility of arteriovenous anastomotic ehatinols
opening to permit a more rapid imlmonnry blood flow in the horizontal ])Osition is sug-
gested. Sayen.

Holmgren, E, S.: The Movements of the Mitro-Aortlc Ring Recorded Simnltanconsly by
Cineioentgenography and Electrocardiography. Acta rndiol. 27; 171 (No. 2) 194«.

The movements of a sharply outlined calcific deposit in the mitral valve ring were
studied in two patients bj' making cineroentgenogrnms at IG frames per second and
simultaneously recording an eleetrocardiogram with a signal marking the time of the
successive exposures. It was found that the calcific .shadow moved npicnlly ,iust after
^ the beginning of the QRS complex and continued to do so until the end of the T wave.
During the latter part of the isoelectric period the .shadow moved slowly back toward
the base, stopped briefly at the beginning of the P wave, and then moved a little farther
basally until just after the beginning of the next ventricular complex. The total distance
traveled was about 2 cm.; a considerably greater distance than the amplitude of the
ventricular wall pulsation. Thus, the mitral ring appeared to move upward toward the
base with auricular systole and downward toward the apex with ventricular s^-stole,
which was in accord with other observations in the literature. Sayen

Bernstein, O.; Treatment of Acute Arrhythmias During Anesthesia hy Intravenous
Procaine. Anesthesiology 7; 113 (March) 194G.

Previous experimental data have shown that the intra\enous or intracardiac injec-
tion of procaine into anesthetized dogs which had developed serious cardiac arrhythmias

SEI^ECTED .MJSTRACTS : , • ' 271 •

. resulted iii. recovery and I'csto ration of noniml rliytlim. It is emphasized that thelihtra- . .
venous injection of procaine or other local anesthetic agents is to he scrupulously avoided ’

'■ in the conscious patient, in -whom it may produce cardiovascular collapse or. stimulation .
of the central nervous- system to the point of generalized comuilsions. However, .the
tolerance to procaine in the anesthetized subject is different from that of unanesthetized
, ■ ihdi\’iduals. In experimental work on dogs anesthetized 'with cyclopropane, loO mg. of , .

.procaine was injected intravenously without any e\ddence of untoward effects.

' In the series of patients rejjorted by the author, the single dose of procaine used

in the anesthetized patient ranged from SO to 70 milligrams. Ho deleterious effects were,
observed; on the .contrary, cardiocirculatory improvement was often effected. The author
related his experience with single-dose injections intravenously into fourteen anesthetized
' • patients with acute arrhythmias during intrathoracic operations. The arrhj-thmias always
improved dramatically.

The use of procaine during anesthesia to diminish cardiac irritability was based ;

. upon a number of findings. Investigators have shoAvn that pfocaihe applied locally to
' the heart reduced the irritabibty of the myocardium. It has also been established that
during chloroform anesthesia the injection of procaine protects against the development
of ventricular fibrillation produced by epinephrine. Cardiac arrhythmias produced by
' epinephrine during cyclopropane anesthesia in dogs can be abolished by procaine after
such arrhythmias have been established. Previous studies have also shown that when the
, ventricular fibrillation sets in during cyclopropone anesthesia, the intracardiac injection

■ of procaine is usually followed by a return of sinus rhythm. - , ‘

■ ' In discussing the efficacy of the use of procaine, it is stated that general anesthesia -

probably affords specific protection against the stimulating action of procaine on the ■
central nervous system. . Further studies are needed, however, to determine the optimal - ,

. dose, ‘ Bei/I/Et.

Noble, B, P,, ' Gregersen, M. I., Porter, P. M., and Buckman, A.i Blood Volume in
Clinical Shock, H. The Extent and Cause of Blood Volume Eeduction in Traumatic
Hemorrhagic and Burn Shock. .T. Clin. Investigation 25: 172 (May) 1946. .

The mechanism of traumatic shock is similar to that of hemorrhagic shock in that
the plasma ' proteins and the erythrocytes alike are lost from the circulating blood in
. , proportional amounts, and hemodilution occurs to compensate for the reduction in circulat- .
ing blood volume. The inference is that severe skeletal trauma is accompanied by loss
of whole blood into the injured tissues and that a generalized increase in capillary V
permeability does not occur in these conditions. On the contrary, burn shock and peri^.,,
tonitis are accompanied by homoconcentration due to loss of plasma at the. site of injury.

■ ; ’ ■ ^ ^ . PRIEDLAND. .

Weens, H. S., and Heyman, A.: Cardiac Enlargement In Fever Therapy Induced. by Intra-
venous Injection of TjTDhoid Vaccine. Arch. Int’ Med. 77: 307 (March) 19,46.

The effects of febrile illnesses upon the heart, particularly in the precipitation of ,

' ' heart failure, are discussed by the authors. During the treatment of patients with neuro-

syphilis ; with , fever ' induced by intravenous administration of typhoid, vaccine, . these' '

■ authors observed roentgenographic evidence of cardiac, enlargement in , a significant num- '
ber; of cases.' Cardiac enlargement was .pi’esent in eight of fifteen patients during the ' =

, : period of fe'ver therapy. Increases in .the transverse diameter varying from ! to 2.3 ,cmi ‘

. were observed. In 'two patients there 'was associated pulmonary congestion. ’• . '

; . , ' The, increase in the- heart size was , usually recognized by the end of the first ■vyeek ‘

but was more pronounced after the second or , third Vweek of therapy. Eegre^sion. of ' .
the increased, heart size usually, occurred during the month -following fever, ' BELi t

272

AMERICAN HEART JOURNAL.

Cosgrove, E. F., and Caravati, C. M.: Salicylate Toxicity; The Prohahlc Mechanism of
Its Action. Ann. Int. Med. 24: 38 (April) 1940.

The recent vogue for massive salicylate therapy in rheumatic fever has introduced
several problems, one of vrhich is the trouble.some nau-sca and vomiting ivhich develop.^
during treatment. The purpose of this study was to determine whether such symptom.s'
are duo to the action of the drug upon the gastrointestinal mucosa or to a central stimula-
tion of the vomiting center. To tost the validity of each view, data were compiled from
gastroscopic examinations, estimations of the salicylate level in the blood, determination
of the concentration of salicylic acid in the gastric aspirates, and analyses of salicylate in
the urine before and after administration o? alkalies. According to the authors, the
results in a limited number of patients indicated that nausea was experienced more often
by patients who received the drug intravenously than by those who received it orally, and
that a definite correlation could bo established between the nausea and a critical level
of the salicylate concentration in the blood. Tt was observed also (hat the administra-
tion of alkalies relieved the nausea in the group receiving the drug intravenously as well
as in those who received it by mouth. The factor presumed to bo responsible for this
relief was increased urinary excretion of salicylate which followed the administration of
the alkali. Finally, it was observed that salicylic acid was absent in the gastric aspirates
of patients in whom the blood level of ."lalicylnte was high, and by gastric examination
no gastric lesions could be seen in those receiving mas^sivc doses of salicylate, cither orally
.or intravenously. The authors conclude that the gastrointestinal symptoms which appear
during massive salicylate therapy are due to the action of the drug on the cerebral nerve
centers and not to any local otTcct on the alimentary tract. Wkkukos.

Whitehom, W, V., Bdelmann, A., and Hitchcock. F. A.: The C-ardlovascuIar Ecsponses to
the Breathing of 100 Per Cent Oxygen at Normal Barometric Pressure. Am. .T.
Physiol. 146: G1 (April) 1940.

Following a fiftoen-niinutc rest period, normal subjects breathed 100 per cent
oxygon for sixty minutes. The cardiac output was determined by the ballistocardiographic
method. A significant reduction in cardiac output, amounting to -0.G3 to -0.98 litcr.s
per minute, was observed; the percentage change was -1.3 per cent to -19,4 per cent.
Subjects breathing room air for a sixty-minute period displayed smaller changes in
cardiac output amounting to -O.OG to 0.22 liters per minute; the percentage change was
-1.3 to -4.9 per cent. These latter figures were considered to have no statistical value.
The reduction in cardiac output was elTocted by means of a decline both in the heart rate
and in stroke volume. Systolic arterial pressure did not change significantly; however,
at the end of the sixty-minute tost period, diastolic prcs.surc averaged 7 mm. Hg higher
than the control value. FaiEnnAND.

DeLaBarreda, P.: The Significance of Cardiac Weight in Bats With Experimental Hyper-
tension. Bov. din. espnii. 19: 167 (Nov. 15) 1945.

Hypertension was produced in rats by the use of Goldblatt's clamp and the produc-
tion of cellophane perinephritis. After hypertension had become cstabli.shod, the cardiac
and total body weights were correlated in accordance with Addis’ formula. Normal
animals were used as controls. Although cardiac hypertrophy usually develops with per-
sistent experimental hypertension, the author found that In'portropliy does not always
occur. Moreover, hypertrophy was sometimes found in normal rats without hypertension.
Hence, the determination of cardiac weights is not an adequate criterion of the past
status of the arterial hypertension. Goii)

f

SELECTED ABSTRACTS '

273 '

Repetto, R., Terrari, J. A., and Benzecri, I.: Ruptxxre of Aortic Valves Due to Effort;

Prensa m4d. argent. 44: 2171 (Nov. 2) 1945. V. /

I

A case of rupture of the leaflets of the aortic valve following sudden severe effort
is reported. The authors distinguish between rupture due to effort and that caused -by-
trauma to the chest. In the former the lesion occurs at the angle of attachment of the
leaflets to, the aortic wall while in the latter the rent occurs at. the free valvular margins. .
-The characteristic murmur is heard at some distance from the heart in rupture due to
effort, while in trauma to the chest it is usually confined to the precordium. The rup-
ture is due to sudden increase in the intra-aortic pressure and the inability of the valves
to withstand the augmented diastolic recoil of the column of blood. Antecedent disease
such as atherosclerosis or syphilis increases the vulnerability of the valves. The increase
in the aortic pressure is the result of increased cardiac output following increased venous
return which occurs during the deep breathing that precedes sustained effort, the fixation
, of the chest and the squeezing of the subclavian and carotid vessels by the contracted
muscles of the neck, shoulders, and arms, and the outpouring of adrenalin during effort.

The characteristic sign and symptom is the murmur of which the patient as well
as his neighbors may become acutely aware, and whicli is best described as the “cooing
of a dove.“

Finally, the authors call attention to a symptom-free period lasting from minutes
to weeks that may occur between the causative effort or trauma and the appearance of
the characteristic murmur. Its recognition is important from the legal standpoint, since
total disability follows rupture of the aortic valves.. Left ventricular enlargement and
failure occur sooner or later in the course of the disease, and subacute bacterial endo-
carditis may be a complication. In the early period, both the electrocardiogram and the
x-ray studies of the heart are negative. Gold.

Stryker, W. A.: Coronary Occlusive Disease in Infants and Children. Am. J. Dis. Child.

71: 280 (March) 1946.

Considerable interest has been aroused recently in the incidence of coronary occlu-
sive disease in young soldiers. The importance and nature of coronary occlusive disease
in a still younger age group, namely, that of infants and children, has not been fully
appreciated. In adults, the great majority of coronary occlusions are related to arterio-
sclerotic disease of the atheromatous type. In infants and children, however, that type
of arteriosclerosis is a relatively rare factor in causing occlusion and the incidence of
other types is increased. The arterial lesions which may produce partial or complete
occlusion in infants and children include medial calcification with fibroplastic prolifera-
tion of the intima, polyarteritis (periarteritis nodosa), syphilitic arteritis, embolism, con- ■
genital abnormalities, rheumatic arteritis, and hypertension. Stryker reports the findings
in a series of hearts from nine infants and children under the age of 17 years, in whom
occlusion of one or more coronary artei-ies is the important feature. He discusses each
■ of the above categories and illustrates them with sections of the coronary arteries show-
ing the different types of pathology producing coronary occlusion. Bellet.

Wlntrohe, M. M.: The Cardiovascular System in Anemia, With a Note on the Particular

Abnormality of Sickle Cell Anemia. J. Hemat. 1: 121 (March) 3946.

The author reviews the cardiovascular and physiologic adjustments which occur in
the presence of anemia. These include increase in the cardiac rate, velocity of blood
flow, minute volume, cardiac output, cardiac size, oxygen utilization and oxygen consump-
tion; and decrease in the circulation time, the blood viscosity, the arterial blood pressure,
the total blood' volumcj the A-V oxygen difference, and the vital capacity of the lungs.

: He suggests that the remarkable changes found in the cardiovascular system in cases of
sickle coll anemia may bo tlie result of adjustment to severe anemia of exceptional
. chronicity. • , ' . -r,,™ .

274

AMERICAK HEART .TOURNAL

Pereiras E., and Castellanos, A.: A New Indirect Radiologic Sign in the Diagnosis of
. Aortic Coarctation by Means of the Superior Retrograde Aortography. Rev. cul)ana

de Cardiol. 99: 120, 1945.

Tliis procedure of retrograde aortogrnphj' is based upon the existence of aimstamoais
between the lateral thoracic, the superior intercostal and the internal nuimmarj’ arteries
arising from the aorta. Marked dilatation and tortuosity of tlio.se vo.sscls are oonsidored as
pathognomonic of coarctation of the aorta. The notching along the inferior border of the
rib is shown to bo produced by the looping of the dilated intorco.stal ve.s«el.s.

The authors’ technique is as follows: a tight tourniquet is applied to the left arm
distal to the site of injection. Twenty cubic centimeter.s of oO per cent diodrast or ncoio-
pax is then injected into the left brachial artery at the antecubital fossa. Considerable
lesistanco is usually encountered in overcoming the arlorial blood pressure. No inci.sion
of the skin is necessary as a Lindemann catheter is used.

Usually the subclavian artery and part of the aorta are visualized occasionally the
abdominal aorta is scon. This technique was fir.st tried in newborn infants but has since
been used successfully in older children and adult.s without ill cfTccf. Tavitas

Firestone, G. M.; Meningococcus Endocarditis. Am. .T. Jf. Sc. 211: .5.5G (May) 394d.

Although moningococcic infections arc susceptible to the newer therapeutic agent.s.
the fulminating character of the infection when it afTeets the valves of the heart, com-
bined with the difficulties involved in establishing an early bacteriologic diagnosis, often
conspire to delay therapy until the patient’s condition is beyond (ho point of rover.«ibility.
The author describes in detail the clinical features of one case of mcniugococcic endo-
carditis, together with an analysis of twenty-four cases collected from the literature. He
believes that the clinical picture is quite characteristic of this bactoriologically .specific
typo of acute endocarditis; so much so that one may often obtain, in individual case.«.
a definite clue as to the etiological diagnosis. Sfost characteristic arc the presence of
skin lesions, arthralgia, and a tertian, quartan, or double quotidian t,vpo of temperature
curve, together with the symptoms and signs of acute septicemia and physical signs of
cardiac valvular involvement. Ditiakt.

Shanno, R. L.: Rutin: A New Drug for the Treatment of Increased Capillary Fragility.

Am. J. M. Sc.' 211; 539 (May) 1940.

Rutin, which is probably the active .cubstance in citrin, is a crystalline glueosidc
of quercetin and a derivative of flavonc. It is without either acute or chronic toxic
effects when administered to animals. The author has experiraentod in human being.s
with this substance in doses of '20 mg. (occasionally liigher) three times a day to deter-
mine its effectiveness in controlling increased capillary fragility as determined by the
Gothlin test. No toxic effects wore observed. Of thirteen hj’pertonsive patients with
increased capillary fragility all improved when treated ivith rutin. Eleven nddition.al
hypertensive patients received thiocyanate plus rutin. .‘Seven of this group had jiormal
'fragility which was maintained by the prophylactic use of rutin with thiocyanate. Two
patients treated solely ^vith thiocyanate developed an increase ia the Gothlin index, wliich
became normal following treatment witli rutin. One maintained a normal index on
thiocyanate after an abnormal index had previously been created by rutin. Two cases of
pulmonary hemorrhage of undetermined origin with increased capillary fragility wore
treated with rutin which restored a normal index and ended the bleeding. In three
cases of increased capillary fragility, uncertain results were obtained due to drug reac-
tions. One case of small hemorrhage into the eighth nerve nucleus and one with complete
heart block and retinal hemorrhages returned to normal with rutin therapy.

It is concluded that rutin appears to bo of value in: preventing vascular accidents
in patients with hypertension, maintaining normal capillary fragility, avoiding vascular
accidents in patients being treated with thiocyanate, and controlling pulmonary bleeding
3f undetermined oriein. „

^ Dckaot.

Book Reviews

INFECCAO Reumatica E. Careitb Reumatica. By Moacir Carlos Barroso, Capitao Medico do
Exercito. Grafica Laemmert Limitada, Rio de Janeiro, Brazil, 1945, 182 pages, , 71
illustrations..

Tins nioiiograpli includes tlie personal experience of tlic author with rheumatic fever and .
rheumatic heart disease in a military hospital in Uruguayana in the Southern Brazilian state of ,
Rio Grande do Sul. It also quotes the experience of Pedro da Cunha and his associates in Rio dc
Janeiro. A well-written and documented account is given of rheumatic fever and rheumatic -
heart disease. So far as we are aware, it is the most extensive review of the subject in
Portuguese. Thus, the monograph is of considerable importance.

Of interest is the attention given by the author to the fact that,, in the temperate zone
areas of Brazil, there is a high incidence of rheumatic fever. This incidence is considered
-similar to that of other countries of like climates. In Brazil, the clinician has long been
taught to tliink first of sj’philis. A weU-timed plea is presented for the clinician to remember
that rheumatic fever is common and should not be neglected. The monograph deserves a nude
circulation, and it will doubtless serve a most useful purpose.

Paul Schlesevoer, M.D., and T. Duckett Jones, M.D.

Cornell Conferences on Therapy. Edited by Han-y Gold, David P. Barr, McKeen Cattell, ,
Eugene P. DuBois, and Cliarles TI. Wheeler. Now York, 1946, The Macmillan Company,
vol. I, 322 pages.

In tliis book are contained what might be called teacliing conferences given at Cornell to '
the undergraduates in medicine. Many will be fanuliar with this type of presentation as a
number of these conferences have already appeared in the Journal of The American Medical .
Association’ and the Neio York State Journal of Medicine.

. ' Designed to bridge the gap between the teaching of Pharmacology and of Therapeutics, ..
iiiembers of the former department combine with doctors from the clinical departments to
make the presentations, which arc made in the form of a brief lecture followed by questions /
and answers. , Drug therapy is discussed chiefly, but other forms of therapy, such as bed rest, '
are also covered. Apparently, further volumes are planned; the subject matter of this volume
caimot be, classified under one head.

The book can be highly recommended as a statement of modern therapeutic ideas.

. Isaac Starr

American Heart Association, Inc.

1790 Broadway at 58Tit Street, Nev.' York, N. Y.

Dr. kot W. Scott
President

Dr. Howard F. West
yicc-Prc,^!dcn(

Dr. Gnonan R. Herrmank
Treasurer

Dr. Howard B. SraAoon
fSccretarp

BOARD OP DIRECTORS

*Dr. Edgar V. Alden Rochester, Minn.
DR. Arlie R. Barnes Roche.'Jtcr, Minn.
Dr. WiLLiAJt H. Bunn ,

Younustown, Ohio

Dr. Clarence tie la Chapelle

New Vork City
DR. Norman E. Freeman Phllatlclphin
»Dr. Tinsley R. Harrison Dallas

Dr. George R. Herrmann Galveston
Dr. T. Duckett Jones Boston

DR. LOUIS N. ICATZ ChlCREO

•Dr. Samuel A. Levine Boston

Dr. Gilbert Marquardt Chicago

♦Dr. H. M. Marvin New Haven

•Dr. Edwin P. Matnard, Jr. Brooklyn
♦Dr. Thomas JL McMillan Philadelphia
Dr. Jonathan JIeakins Montreal

Dr. E. Sterling Nichol Mlnml

♦Executive Committee

Dr. Harold E B. Pardee

New York City
Dr. William B. Porter Richmond, Va.
Du. David D. Rutstein New York City
•Dr. .lOHN .1. Sampson San FrancKsto
•Dr. Roy- W. Scott Cleveland

Dn. Fred M. Smith Iowa City

Dr. Howard B. Spraoue Boston

Dr. GroROE F. Strong

Vancouver, B.C.. Can.
Dr. Wili.iam D. Stroud Philadelphia
Dr. Homer F. Swift New Y'ork Clt>’
Dr. William P. Thompson Angelti
Dn. Harry E. Unoerleider

New York Clty
•Dr. Howard F. West Iajs Angelos
Dn. I’AUL D. White Boston

Dr. Frank N. Wilson Ann Arboi

•Dn. iRVi.NG S. Wright New York City
Dr, Wai.lace M. Yatl-r

Washington, D. C.

DR. H. M. Marwn, Actinp Eaccutivc Secretary
Anna S. Wright, Office Secretary
Telephone, Circle 5-8000

T he American Heart Association is tho only national orpaniralion devoted to
educational work relating to diseases of the heart. Its activities are under
the control and guidance of a Board of Directors composed of thirty-three eminent
physicians who represent every portion of the country.

A central office is maintained for the coordination and distribution of im|)ortnnt
information. From it there issues a steady stream of books, pamphlets, charts,
films, lantern slides, and similar educational material concerned with the recognition,
prevention, or treatment of diseases of the heart, which arc now the loading cause of
death in the United States. The American Heart Journal is under the editorial
supervision of the Association.

The Section for the Study of the Peripheral Circulation was organired in 1935
for the purpose of stimulating interest in investigation of nil tj-pcs of diseases of
the blood and Ijanph vessds and of problems concerning the circulation of blood
and lymph. Anj' physician or investigator may become a member of tlio section
after election to the American Heart Association and payment of dues to that
organization.

The income from membership and donations provides the sole financial support
of the Association. Lack of adequate funds seriously hampers more intensive
educational activity and the support of important investigative work.

Annual membership is $5.00. Journal membership at $11.00 includes a year’s
subscription to the American Heart JournAl (January-December) and annual
membership in the Association. The Journal alone is $10.00 per year.

The Association earnestly solicits your support and suggestions for its work.
Membership application blanks will be sent on request. Donations will be gratefully
received and promptly acknowledged.

276

278

AMERICAN HEART JOURNAL

with, and little interest in, mathematical attacks upon physical problems of the
sort encountered in attempts to apply the classical theory of electricity to the
analysis of the varying electrical field associated with the heartbeat. In theo-
retical investigations of this kind the actual situation under consideration is
always far more complicated than any of those that can be treated mathematically,
and it is necessary to make many simplifying assumptions that are not strictly
in accord with the facts. To assert that all deductions based on such assumptions
are ipso facto worthless is, so to speak, to deny that mathematics has contributed
anything worth while to the physical sciences. To maintain, on the other hand,
that deductions of this kind represent anything more than a first appro.ximation
to the truth or have any great value except in so far as they are supported by
experience and by experiments designed to test their validity would be equally
unreasonable. It is imperative that those who make use of conclusions of this
sort as a guide to further investigations, or who attempt to extend them, clearly
understand and constantly bear in mind the postulates upon which they rest.

Most of the controversies to which Einthoven’s work has given rise seem to
have originated in differences between the participants in respect to their famili-
arity with and their attitude toward its theoretical background. In our opinion,
there is no reason to suppose either that Einthoven and his associates had any
false notions as to the general character of the heart’s electrical field or that they
considered their method of determining the position of the electrical axis of the
heart entirely free of error. In 1921, a paper by Lewis, Drury, and Iliescu*
on the electrical axis of the auricle in clinical cases of auricular flutter raised a
question as to the conditions under which the principles of Einthoven’s triangle
are applicable. A letter to Einthoven concerning this matter was answered
by him on Nov. 21, 1921, as follows:

“In regard to the equilateral triangle I fully agree with you. I assumed
in my original paper ‘Ueber die Richtung und die Manifeste Grdsse der Poten-
tialschwankungen etc.,’ in the center of the triangle a ‘bipole,’ that is to say two
points lying very close together and showing a potential difference. The triangle
was supposed to be a homogeneous sheet of conducting material and in regard to
the distance between the two points of the bipole, of a large, let us say infinite
extent.

“The applicability of this scheme to the ordinary leads of the human body
depends indeed on the fact that the electrodes are at a relatively great distance
from the heart. If they are placed near the heart the errors are greater and the
more so the closer they get to the heart. Even in the case of the ordinary'' leads
from the limbs the results cannot be absolutely exact.’’

_ A number of attempts have been made to test the validity of Einthoven’s
triangle by impressing a constant or variable voltage upon ttvo metallic elec-
trodes thrust into the heart of a cadaver and comparing the position of the elec-
trical axis, computed by Einthoven’s method from the potential differences
recorded m the standard limb leads, with the direction of the impressed potential
difference. The first experiment of this kind was performed by Fahr and
eber.- ihe heart was exposed and two small zinc needles were thrust into its

WILSONET AL. : EIN.THOVEN’s TRIANGLE, UNJrOLAR LEADS, . ECG , >, 279 .

wall, one in the region of the sinus node and the other at the apex. ‘When
1/5 volt was applied to these electrodes the deflection in Lead I was 10 min., '

; that in Lead II was 46 mm., and that in Lead III was 36 millimeters. The angle
between the line defined by the two electrodes and the direction defined by Lead I '
was estimated at 75 degrees. The corresponding angle computed from (he
deflections in the three leads was approximately 3 degrees larger.

A similar experiment was performed by Wagnei"* on the cadaver of an infant
who had died eight days after birth. In this instance two zinc needles were
thrust through the precordial tiissues into the heart and a potential difference
of approximately 6 volts was impressed upon them. Three milliammctens were .
used to measure the resulting potential differences between the extremities. In
the first test the currents in Leads I, II, and III were 6, 10, and 4 ma,, respec-
tively; when the input voltage was increased, these currents rose to 8, 13, and
5 ma., respectively. The chest was then opened, and it was found that one of
the needles had entered the heart near its base, and the other entered just above,
the apex. The currents in the three leads were the same after opening (he
chest as before. When the electrodes were replaced so that the line defined by
them made an angle of approximately 60 degrees with the direction of Ixvid I
the currents in the three leads were 3, 6, and 3 ma., respectively. When the
electrodes were arranged so that the line defined by them made an angle with 1:hc
frontal plane, the currents in the standard leads were 3, 5, and 2 ma, when the
projection of this line on the frontal plane was parallel to Lead II, and 4, 2, and
' —2 ma., respectively, when it was parallel to Lead 1. This experiment and a
large number of experiments on models of various types led Wagner to conclude
(contra Groedel and Straub) that the theory of the equilateral triangle was
in all respects well founded.

On March 1, 1934, Johnston, Ko<5smann, and Wilson*' performed an experi-
ment on the cadaver of a man who had died of carcinoma of the face complicat ed
by pneumonia more than a week before. During the interim, the cadaver had
been stored in the morgue in the supine posture, and it was su.spected tha(. in
addition to pronounced post-mortem changes there had been some gravitation
of the body fluids into the more dorsal tissues. The input electrodes consisted
of two small brass rods, insulated except at the sharpened tip.s and fixed in a
wooden frame. The frame permitted the rods to be moved endwise so that v/hen ,
they were thrust into the precordium the depth of the tip of each rod was in-
dependently adjustable. By means of a rotating contact breaker a potential
difference of approximately 18 volts was rhythmically impressed upon these
electrodes after they were in place. The thickness of the chest, mea.sured
from precordium to back, v.-as 21 centimeters. The electrodes v/ere first thrust
through the chest wail in the third intercostal space, one just to the right and the
other just to the left of the sternum. The depth of the tip of the former (the
negative electrode) was 5,7 cm, and that of the tip of the latter (the positive V
. electrode) w^as 8.8 centimeters. The deflections recorded in Leads I, TI, and ITI,

' measured 26, 12.75, and — 13 mm., respectively. Moving the left leg electrode
to the pubis had no appreciable effect. Increasing the depth of the positive elec-

AMKRICAK heart JOUKN'Af.

270

Norpoth, Ii., and Vagades, K.: Dlsturl)anco8 of the PacomaUor and of Condiictlon In
Addison’s Disease. Ztschr. f. KreislaufVorpcli. 36: G73 (Dec.) 1913.

The literature reporting electrocardiographic findings in Addisoii's disease is re-
viewed. Among the abnormalities reported have been varying degrees of A-V heart bloch,
prolongation of the Q-T interval, low voltage, T-wavo inversion, and, sometimes, RS-T
segment depression. One case is added by the nnthor,«. 'Iho patient nas a 31-ycar-old
man, with a minor grade of A-V heart block in which the 1^*R interval shortened, to top-
normal duration with exercise. During a sub.seqncnt crisis sinus arrhythmia, brady-
cardia, extrasystoles, and periods of ' sinonnrlenlar heart bhx’k or A*V nodal rhj'thrn
appeared. All of these ubnorniaUties disappeared following the administration of cortical
hormone. ' Sayex.

von Dirlngsiiol'en, H., Sane, H., and Strnad, W,: Study of the Roentgen Density of the
Lungs in Humans as a Measure of the Pulmonary Blood Plow. 2t.schr. f. Kreis-
laufCorsch. 35; 402 (Aug.) 1943,

The authors believe that variations in the roentgen density of the peripheral lung
Held in excess of those occurring with normal respirntion should provide an index of the
pulmonary blood content. Their method was to moiisuvc the ilhiinination of a portion
of the right lung by a pliotoclecfnc cell in front of a lluori).‘»(‘op!c .'u'roen. P.y the use
of a tilt table, the variation in lung rlen.sity of normal .siibject.s in variou.s po.'.itions could
be studied. The roent’gou density of the lung decrca.sed .•jignifietuitly with .shifts from the
erect to the recumbent position. The head-down ]iositioii increased the density, and light
oxerei.se Imd a similar efTcct. Changes in the degree of density under these conditions
werc'sevcral times greater than those resulting from quiet resjiiratiou, When the breath
was held against a pressure of about one atmosphere, decrease in density wn.s ob.served;
a further decrease in density was ol)scrved to follow shifts from the vertical to the
horizontal position. Administration of low-oxygon mixtures and of adrenalin or hi.stamine
produced no significant ofiTocts. The authors' concluded that, contrary to c.xpectations,
the blood content of the lungs decrease.s in recumbency in spite of incrcn‘<ed venous
return. The mechanism is obscure. The possibility of arteriovenous anastomotic ehatinols
opening to permit a more rapid imlmonnry blood flow in the horizontal ])Osition is sug-
gested. Sayen.

Holmgren, E, S.: The Movements of the Mitro-Aortlc Ring Recorded Simnltanconsly by
Cineioentgenography and Electrocardiography. Acta rndiol. 27; 171 (No. 2) 194«.

The movements of a sharply outlined calcific deposit in the mitral valve ring were
studied in two patients bj' making cineroentgenogrnms at IG frames per second and
simultaneously recording an eleetrocardiogram with a signal marking the time of the
successive exposures. It was found that the calcific .shadow moved npicnlly ,iust after
^ the beginning of the QRS complex and continued to do so until the end of the T wave.
During the latter part of the isoelectric period the .shadow moved slowly back toward
the base, stopped briefly at the beginning of the P wave, and then moved a little farther
basally until just after the beginning of the next ventricular complex. The total distance
traveled was about 2 cm.; a considerably greater distance than the amplitude of the
ventricular wall pulsation. Thus, the mitral ring appeared to move upward toward the
base with auricular systole and downward toward the apex with ventricular s^-stole,
which was in accord with other observations in the literature. Sayen

Bernstein, O.; Treatment of Acute Arrhythmias During Anesthesia hy Intravenous
Procaine. Anesthesiology 7; 113 (March) 194G.

Previous experimental data have shown that the intra\enous or intracardiac injec-
tion of procaine into anesthetized dogs which had developed serious cardiac arrhythmias

WILSON ET AL. : EINTHOVEN'S TRIANGLE, UNIPOLAR LEADS, ECG ^ 281

that of a dipole of doublet located in a homogeneous isotropic medium of large
extent. In all probability this view was suggested by a well-known theorem
on the potential of a complex of electric charges distributed in a dielectric and
enclosed by a spherical surface of the smallest adequate radius. The potential
of such a complex at any point outside this surface may be expressed in the form
of an infinite series of spherical harmonics. When the net charge of the complex
is zero, the successive terms of the series represent the potential of a dipole,
the potential of a quadrapole, the potential of an octupole, and the potentials of
multipoles of increasingly higher order.' At points sufficiently distant from the
center of the sphere the field may legitimately be regarded as closely approaching
that defined by the first term alone, in other words, that of a dipole."

Between the electrical field of a complex of charges of the kind described and
the electrical field associated with the heartbeat, there is an obvious analogy.
The sources and sinks of the heart’s field corresponding to the positive and nega-
tive charges of the complex all lie within a circumscribed region: the smallest
sphere in which the heart can be enclosed. The action current which flows
out of any given cardiac fiber re-enters the same fiber in a neighboring region.
Each source is, therefore, associated with a sink of equal strength, and it is
clear that the cardiac field is not only comparable to that of a distribution in
which the net charge is zero, but to a complex consisting of doublets only. Be-
tween an electrostatic field and the cardiac field there are, however, some obvious
differences. In the first place, the latter, unlike the former, varies with the
time. Nevertheless, the cardiac field at any given instant has always been
treated as if it were stationary; the effects of induction have been neglected.
The justification for this procedure lies in the low frequency of the cardiac cur-
rents, the relatively small size of the conductor involved, and the relatively small
conductivity of the body tissues, and also in the results of experiments of the kind
we have already described in which the distribution of variable currents of low
frequency has been studied. In the second place, the heart is imbedded in a
medium which is neither strictly homogeneous and isotropic nor infinite in extent.
The effect of the requirements imposed by the boundary conditions involved is
to superimpose upon the field of the cardiac sources and sinks, as it would exist
in free space, the field of a layer of doublets at the body surface^ and the fields
that would be produced by the presence of a single layer of charge on every surface
separating tissues of unlike conductivity. The double layer is required to
annul the field of the cardiac sources and sinks outside the body and each of
the single layers to make the product of the conductivity and the electric intensity
normal to the boundary surface the same on both sides of it. The effect of the
double layer will, in general, be greatest at the body surface and least at points
most distant from it; the effect of each single layer will be greatest near the surface
oh, which it lies. It is, of course, out of the question to compute the exact effect
of the boundary conditions that must be met in the case of conductors like the
body which are irregular in shape and complicated as regards the arrangement
and electrical properties of their constituent parts. It is possible, however, to
compute the field of a centric or eccentric doublet in a sphere made up of spherical

280

AMERICAN HEART JOURNAL

trode to 10 cm. and decreasing the depth of the negative electrode to 5 cm.
produced only very minor changes in the potentials of the three e.xtremilies,
measured with respect to that of a central terminal connected to these electrodes
and also to an electrode in the left interscapular region through resistances of
10,000 ohms. This procedure increased the positivity of tlie electrode on the
back from 2 to 4.5 tenths millivolt.

When the positive electrode was in the third intercostal space near the left
sternal edge with its tip 10.7 cm. below the skin, and the negative electrode in
the fourth intercostal space and on the same vertical line but with its tip 5.5
cm. below the skin, the deflections in Leads I, II, and III measured 1.5, — 30.5,
and — 32 mm., respectively. In this case, however, increasing the depth of the
positive electrode to 15 cm. increased the deflection in Lead I to 1 2 and that in
Lead III to — 35 mm. and reduced the deflection in Lead II to — 23 millimeters.
The factor responsible for this unexpected result was not discovered.

These cadaver experiments by different workers support Einthoven’s belief
that when a potential difference is generated between two points lying within or
close to the heart, the deflections in the three standard limb leads are very nearly
proportional to the cosines of the angles made by the frontal projection of the
axis of this potential difference with the corresponding sides of his equilateral
triangle. It is, of course, true that the conductivity of dead tissues is by no
means the same as the conductivity of living tissues. If experiments of the kind
described could be performed on living subjects would the results be vastly
different? In 1920, Wilson and Herrmann® made a crude test of the validity
of Einthoven's triangle in the course of some experiments on dogs in w'hich the
heart was stimulated rhythmically for the purpose of studying its refractory
period. The stimulus was the curtent delivered by the secondary coil of an in-
ductorium when the circuit through the primary coil was broken. Sharp de-
flections representing the induction shocks Avere observed in the limb leads.
A stimulating electrode Avas then attached to each terminal of the secondary
coil and the two electrodes Avere thrust into the \entral wall of the heart, one
near the base and the other near the apex, in such a AA'ay that the line joining
them was nearly parallel to the long axis of the body. The deflections produced
by the induction shocks in the limb leads measured 2, 16, and 14 mm., respectiA^ely,
under these circumstances. When the electrodes were so placed that the line
joining them Avas perpendicular to the long axis of the body, these deflections
measured 9,3, and — 6 mm., respectU'^ely. Except for the response to those shocks
jvhich fell outside the refractory period, the heart continued to beat normally.
Its ventral surface Avas exposed and the luiAgs were not fully inflated. We
doubt that the string gah’-anometer Avas capable of recording the A'ery brief in-
duction shocks Avith great accuracy. NCA^ertheless, it will be noted that the
direction and relative size of the deflections in the limb leads were about AAdiat
would be expected on the basis of the principles of the equilateral triangle.

It is clear that EinthoA'’en regarded the electrical field associated Avith the
heartbeat, in so far as it is represented by the potential differences recorded by
the standard limb leads, as approximately equivalent at any giA^’en instant to

. WILSON ET Ai;. : EINTHOVEN’s TRIANGLE, UNIPOLAR LEADS, EGG . 281

that of a dipole or doublet located in a homogeneous isotropic medium of large : .
extent. In all probability this view was suggested by a well-known theorem , ^
on the potential of a complex of electric charges distributed in a dielectric and !
enclosed by a spherical surface of the smallest adequate radius. The potential
of such a complex at any point outside this surface may be expressed in the form
of an infinite series of spherical harmonics. When the net charge of the cornplex
is zero, the successive terms of the series represent the potential of a dipole,
the potential of a quadrapole, the potential of an octupole, and the potentials of
multipoles of increasingly higher order."^ At points sufficiently distant from the
center of the sphere the field may legitimately be regarded as closely approaching
that defined by the first term alone, in other words, that of a dipole.''

Between the electrical field of a complex of charges of the kind described and, ■
the electrical field associated with the heartbeat, there is an obvious analogy.

The sources and sinks of the heart’s field corresponding to the positive and nega-
tive charges of the complex all lie within a circumscribed region: the smallest / .
sphere in which the heart can be enclosed. The action current which flows
out of any given cardiac fiber re-enters the same fiber in a neighboring region.
Each source is, therefore, associated with a sink of equal strength, and it is
clear that the cardiac field is not only comparable to that of a distribution in
which the net charge is zero, but to a complex consisting of doublets only. Be-
tween an electrostatic field and the cardiac field there are, however, some obvious
differences. In the first place, the latter, unlike the former, varies with the
time. Nevertheless, the cardiac field at any given instant has always been'
treated as if it were stationary; the effects of induction have been neglected.

The justification for this procedure lies in the low frequency of the cardiac cur-
rents, the relatively small size of the conductor involved, and the relatively small
conductivity of the body tissues, and also in the results of experiments of the kind
we have already described in which the distribution of variable currents of low .
frequency has been studied. In the second place, the heart is imbedded in a:
medium which is neither strictly homogeneous and isotropic nor infinite in extent.

The effect of the requirements imposed by the boundary conditions involved is
to superimpose upon the field of the cardiac sources and sinks, as it would exist
in free space, the field of a layer of doublets at the body surface® and the fields
that would be produced by the presence of a single layer of charge on every surface
separating tissues of unlike conductivity. The double layer is required to
annul the field of the cardiac sources and sinks outside the body and each of
the single layers to make the product of the conductivity and the electric intensity
normal, to the boundary surface the same on both sides of it. The effect of the
double layer will, in general, be greatest at the body surface and least at points
most distant from it; the effect of each single layer will be greatest near the surface
qri which it lies. It is, of course, out of the question to compute the exact effect
of the boundary conditions that must be met in the case of conductors like the \
body which are irregular in shape and complicated as regards the arrangement -
‘and electrical properties of their constituent parts. It is possible, however, to
compute the field of a centric or eccentric doublet in a sphere made up of spherical '

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shells of specified conductivities. On the basis of such compulations, of the
available experimental knowledge of the specific conductivities of the body tissues,
and of the results of experiments of. the kind described in previous paragraphs
it seems to us that Einthoven’s views as to the nature of the heart’s electric al
field, in so far as they are expressed in, or may be inferred from, his published
work, are still in accord with all the known facts.

UNIPOLAR LEADS

In 1932, Wilson, Macleod, and Barker® described a new type of electro-
cardiographic leads in which a central terminal connected through equal resist-
ances to electrodes on the right arm, left arm, and left leg is paired with an ex-
ploring electrode placed on the precordium or upon any other part of the body.
They held that leads of this kind are essentially unipolar in the sense that they
record the potential variations of the exploring electrode with respect to a refer-
ence point which remains at very nearly the same potential throughout the
cardiac cycle: It was shown that the sum of the differences in potential between
any number of electrodes and a nodal point connected to these electrodes through
equal resistances must be zero as a consequence of Kirchhoff’s first law. The
potential of the central terminal is consequently equal at every instant to the
mean of the potentials of the electrodes on the e.xtremities. On the basis of the
assumptions upon which the equilateral triangle of Einthoven, Fahr, and de
Waart is based plus the additional assumption that electrical forces of cardiac
origin which are perpendicular to the plane of the standard limb leads have no
significant effect upon the potential variations of the extremities, it was also shown
that the potential of a central terminal connected through equal resistances to
electrodes on the right arm, left arm, and left leg is not materially affected by the
heartbeat and may be considered nearly constant throughout the cardiac cycle.

This conclusion promises to become the subject of a controversial discussion
no different in character and not less lengthy than the one that has revolved around
Einthoven’s triangle. Several kinds of experiments bearing on its validity have
been reported. Burger and Wuhrmann^® mention that one of them compared the
potential of the central terminal of Einthoven’s triangle with that of other central
terminals each connected to three electrodes equidistant from the heart and lying
at the apices of a triangle enclosing it. No details are given, but it is slated
that the differences in potential between the various terminals were negligibly
small. Arrighi” is known to have carried out e.\periments of a similar kind.
So far as we know his work has not yet been published, but all of his experiments
that we have knowledge of yielded results comparable to those’ reported by
Burger and Wuhrmann. We have performed one experiment of the same kind
and the results of such experiments are predictable on the basis of Arrighi’s
published work. In his doctoral thesis^® he described his experience with three
leads which formed the sides of a sagittal triangle that enclosed the heart. One
electrode was placed in the left submaxillary region close to the chin, the second
3 or 4 cm. to the left of the ’midpoint of a line joining the umbilicus with the
center of the pubis, and a third in the left interscapular space, approximately at

, WILSON ET AL. : EINTHOVEN’s TRIANGLE, UNIPOLAR LEADS, ECG , 283

the level of the spinous process of the seventh thoracic vertebra. In almost all
of the more than fifty cases of various types that were studied, it was found that
the voltage of the deflection recorded at a given instant in the cardiac cycle
by leading from the electrode on the jaw to that on the abdomen was very nearly
equal to the sum of the simultaneous voltages recorded in Leads II and HI
divided by the square root of 3. It is not difficult to demonstrate algebraically
that whenever this is the case the difference in potential between a central terminal
connected to the usual extremity electrodes and a central terminal connected to
Arrighi’s submaxillary and abdominal electrodes only cannot be appreciably
greater than that between his abdominal electrode and the left leg electrode.
Since these two electrodes are similarly situated with reference to the heart we
may expect that they will always be at nearly the same potential. A lead from,
the central terminal of Einthoven’s triangle to a central terminal connected
to all three of Arfighi’s electrodes will, therefore, ordinarily yield deflections
similar to, but approximately one-third as large as, those obtained by leading
from the first of these terminals to the electrode on the back.

The tracings obtained in the only experiment of this kind that we have carried
out are reproduced in Fig. 1. In addition to the standard and the unipolar limb
leads (taken by Goldberger’s method) the following special leads (taken with the
electrocardiograph at twice the normal sensitivity) are shown: (1) a lead from
the central terminal of the Einthoven triangle to a terminal connected to all three
of the Arrighi electrodes; (2) the same lead after the electrode on the back had
been disconnected from the second terminal; (3) the same lead after reconnecting
the electrode on the back and disconnecting the electrode on the jaw; (4, 5, and 6)
leads from the central terminal of the Einthoven triangle to each of the three
Arrighi electrodes in turn; (7) a lead from the same terminal to one connected
through equal resistances to two electrodes, one on the left back near the base
' of the neck and the other just to the left of the sacrum ; (8 and 9) leads from the
same terminal to each of these electrodes in turn. It will be noted that the
greatest potential difference between the central terminal of the Einthoven
triangle and that of the Arrighi triangle did not exceed 0.15 mv and that the
first of these terminals was negative with respect to the other. It should also be
V noted that the deflections of Lead Vt', — Vt are similar to those of Lead Vb — Vt
but about one- third as large.

In the case of normal subjects, an electrode placed on the back directly
behind the heart is ordinarily positive with respect to the central terminal of the
Einthoven triangle throughout the greater part of the QRS interval; For the
' time, being we may assume, therefore, that this terminal is normally slightly
: negative and that of the Arrighi triangle slightly positive when the sagittal
comporieht of the heart’s electromotive force has an anteroposterior direction.

. By connecting these two terminals together or by connecting an electrode on
the back to the central terminal of Einthoven’s triangle we might perhaps

obtain a reference point more nearly indifferent than either.

■ -Several investigators have attempted to ascertain the magnitude of the
• potential variations of the central terminal of Einthoven’s triangle by means of

WILSON ET AL. ; EINTHOVEN’s' TRIANGLE,, UNIPOLAR LEADS; ECG ' . , 285-;

immersion experiments. Eckey nnd Frohlich^^ placed their subjects in a large
wooden tub lined with metal and filled with distilled. water; contact between the ,
subject and the metal lining was prevented by a suitable wooden support. The
surface of the water was screened by a sheet of metal placed beneath it and in
contact with the metal lining of the tub. The subject breathed through a glass
tube brought out tlirough a small hole in this metal lid; other small openings
accommodated the electrocardiographic cables. The electrodes employed were
not insulated. It was found that immersion of the subject in distilled water
did not materially reduce the size of the deflections in the standard limb leads •
and tJiat the cardiac field did not extend to the water outside the metal screen.
The largest potential variations of the central terminal with respect to this screen
were of the order of 0.2 to 0.3 mv in all of the unspecified number of experiments
performed. . ^

Burger^^ employed a tub lined with zinc and filled with tap water, and he
did not immerse the face of his subjects. He insulated his electrodes from the
bath with rubber sheeting. Immersion reduced the deflections of the standard
limb leads to approximately 75 per cent of their original size. In five experim.ents
on normal subjects the voltage of the largest deflection obtained by leading from.
the metal screen to the central terminal was about 0.26 millivolts. In four of the
five cases the central terminal was slightly negative with respect to the zinc shield
during the greater part of the QRS interval.

We have performed one immersion experiment of a somewhat different kind.
After the standard limb leads had been taken, the subject was immersed up to the
chin in a small fresh-water lake. The short-circuiting effect of the water reduced
the size of the deflections in these leads to approximately one-half their original
size (Fig. 2). There was also a slight change in the form of the ventricular com-
plexes, probably because, when in the water, the subject was not able to assume
exactly the posture in which the control curves were taken. The potential
variations of the limb electrodes and the central terminal with respect to a large
metal electrode suspended in the lake at a distance of about 11 feet from the
body were recorded with an amplifier- type electrocardiograph at twice its normal
sensistivity. The largest potential variation of the central terminal measured
0.15 mv; it was negative to the reference electrode (Fig. 3). The distant and
the left leg electrode remained at practically the same potential throughout the
-cardiac cycle; w-e assume that in a series of experiments this would happen only
rarely. Both arms and a point on the right scapula were negative with respect
to the distant electrode during the greater part of the QRS interval.

Burger was uncertain as to whether the magnitude of the potential varia-
tions of the central terminal could be ascertained by the method which he enir
ployed for this purpose. Wolferth and Livezey’^ have expressed the opinion that
“the reason advanced by Eckey and Frohlich to support the claim that their
immersion procedure can be used to obtain unipolar leads, has no merit.’’ The
lack of agreement exemplified by this comment is basically similar in origin to the
controversy between the proponents of the “negativity hypothesis’’ and the pro-
ponents of the “doublet hypothesis” which, began some ten years ago. As the '

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years have passed it has become more and more apparent that the chief sources
of this controversy are differences in point of view, in opinion as to the proper
choice of a reference point for the measurement of bio-electric fields, and in the
sense in which the word ‘‘potential” is employed between those who are mainly
interested in the action currents of isolated nerves bounded by a dielectric and
those who are mainly concerned with the action currents of the heart which is
imbedded in a conducting medium.* Because many who do not understand the
nature of the dispute have become uncertain as to whether unipolar precordial
and unipolar limb leads are desirable and as to whether they are theoretically
or practically possible, we have re-examined and attempted to clarify the ideas
upon which the concept of an indifferent electrode is founded.

I'ig. 2. Electrocardiograms of a normal subject taken ■with the electrocardiograph
at t\\Ice the normal sensltitdty (2 cm. equals 1 mv).

The sequence of events and the considerations which led to the introduction
of the central terminal for the purpose of obtaining unipolar leads are in outline
quite simple. In 1916, Lewis and Rothschild^’' had difficulty in recognizing the
‘‘intrinsic ’ deflection in leads in which paired contacts were placed on the exposed
ventricular surface. They attributed this difficulty to the arrival of the impulse
beneath both electrodes almost simultaneously. To avoid it they left one elec-
trode in place and moved the other, sometimes to another part of the heart’s
surface, and sometimes to the chest wall. They found the last procedure par-

uegaU\'ity hypothesis” focus their attention upon the action potential,
across tho cell membrane during excitation and therefore choose an injured
region nlilM IS of responding to the excitatory process as their reference point. (For a dis-

cus-ion Cal and Curtis i«) Cardiologists who are forced to deal with tho distribu-

yy‘’*'ants in a volume conductor are confronted by problems of an entirely
^1^® same principles to the interpretation of their tracings, must use
seM^fO ttmir purpos^'^ diflerent sense, and, consequently, must find another point of reference more

288

AMERICAN HEART JOURNAL

ticularly serviceable, and they clearly regarded the chest contact as without in-
fluence upon the position of the intrinsic deflection in the QRS interval. It is
not certain that they considered this contact as indifferent in other respects; or
that they believed the potential variations of this contact too small to have any
significant influence upon the form of the tracings they obtained. In this labora-
tory the electrocardiograph is employed at one-twentieth of its normal sensitivity
Avhen leads of the kind in question are taken. So long as the distant contact
is not placed close to the heart, its location can, therefore, have no important
effect upon the size or form of the deflections recorded. On the other hand,
moving the direct contact from one part of the heart’s surface to another is almost
certain to give the resulting curve an entirely different character. If we think
of the cardiac field in terms of the current density, it is obvious that it is very
intense in the vicinity of the epicardial surface, and, in comparison, of negligible
strength in the neighborhood of the distant electrode. In the former region,
the variations in the intensity of the field during the cardiac cycle are very large;
in the latter they are very small. It is logical, therefore, when employing leads
of this sort, to regard the potential variations recorded as characteristic of the
region upon which the direct contact rests and to think of the distant electrode
as indifferent and without influence upon the form of the curve; in other words,
to consider leads of this kind unipolar.

In 1920, Wilson and Herrmann^® performed the following experiment.
A line was drawn from the fourth left costal cartilage to a point on the left leg
just below Poupart’s ligament. A small electrode (A) was placed at the upper
end of this line and similar electrodes (B, C, D, and E) were spaced along its course
at points 5, 10, 15, and 20 inches, respectively, below the first. With the electro-
cardiograph at half the normal sensitivity. Leads A-B, B-C, C-D, and D-E were
then taken. The largest QRS deflection measured 20 mm. in the first, about
3 mm. in the second, and about 1 mm. in the third of these leads. No deflection
of any kind was visible in the fourth. The results of this experiment suggested
that, if an electrode on the central part of the precordium were paired with a
contact at a considerable distance from the heart, the form and size of the ventric-
ular deflections obtained would be nearly the same regardless of whether the
second electrode were above, below, to the right of, to the left of, or behind this
organ. The experiment was tried and this conclusion was confirmed .i® Theo-
retical considerations and the resemblance in general contour between the ven-
tricular complexes of leads in which a precordial electrode was paired with a
contact far from the heart and those which Lewis and Rothschild obtained by
leading from the epicardial surface of the exposed ventricles to some point on the
chest wall led to the belief that leads of this kind are actually semidirect leads
from the anterior ventricular surface, and this conclusion was published by
'Wilson, Wishart, and Herrmann®® in 1926. A preliminary report of experimental
and clinical observations bearing upon the value of such leads for the purpose
of differentiating left from right bundle branch block was published in 1930 by
Macleod, Wilson, and Barker.®^ The publication of the complete account®®
of these observations was postponed until the components of the human pre-

WILSON ET AL,: EINTHOVEN's TRIANGLE, UNIPOLAR LEADS, ECG 289 '

cordial curves which could legitimately be ascribed to potential variations of the ,
distant electrode,-’ which had been placed on the left leg, could be computed and
eliminated. The central terminal was introduced® with the object of accomplish-
ing the sariie purpose more directly by reducing the potential variations of the
reference contact to a minimum. This seemed desirable in order to make pre-
cordial leads of the kind in question as nearly unipolar, and therefore as nearly
comparable to direct leads of the sort used by Lewis and Rothschild, as might be
possible.

The central terminal is founded upon the idea that, so far as the limb leads
are concerned, tlie electrical field of the heart is approximately equivalent to
that of a dipole lying in or near the plane of these leads and that the principles ,
upon which Einthoven’s equilateral triangle is based are sound. If this view is
tenable the potential of this terminal should remain at nearly the same level
throughout the cardiac cycle. It is true that the sum of the potentials at the,
apices of an equilateral triangle enclosing a centric dipole which varies in strength , ,
will not remain constant unless the plane which passes through the dipole and is •
perpendicular to its axis separates the conducting medium involved into two
identical parts. It is also true that the body is not symmetric with respect to
any plane that passes through the heart. On the other hand, the magnitude of the
effects produced by a lack of symmetry with respect to any such plane must de-
crease as the distances from the heart to the boundaries responsible for it .
increase. It was shown, for example, by Wilson^® that when a coil of copper wire
is placed in the field generated in a layer of electrolyte by a centric source and
sink close together, the resulting modification of the field increases as the dis- .
tUrbing factor is brought closer to the region where the current density is maximal.

\yith respect to immersion experiments and the like, it is evident that factors
which increase the asymmetry of the conducting medium surrounding the hypo-
thetical cardiac dipole will tend to increase, and factors that have the opposite
effect to decrease the potential variations of the central terminal with reference .
to a point that is completel)'' indifferent.. Placing the body in a lake or in a
smaller body of water bounded by a metal screen, cannot change the location
of the boundaries which define differences in tissue conductivity and it is hardly
possible that it can significantly increase the flow of current across them. It
does alter the heart’s field by modifying tlie conditions at the body surface.
The short-circuiting effect of the conducting fluid naturally reduces the potential
differences between the various parts of this surface including those between one
extremity and another and between the extremity electrodes and the centra],
terminal. The magnitude of this effect is proportional to the conductivity of the ■
water in which the body is immersed. The , conductivity of distilled water is
Of the order of 2.x 10'^ mhos per meter and tha^ of lake water and tap water is
five to fifty times as great.'^ If the potential variations of the three extremity v.
electrodes are reduced proportionately and in the same measure as the differences
in potential between them, the potential variations of the central terminal will :
be diminished in the same degree.

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Even when it has comparatively little elTecl upon the size of the deflectit>ns
in tJie limb leads, as in the experiments of Eckey and Erohlich, oi reduces the size
of all these deflections in the same proportion, as in those of Burger, immersion
of the body will not have the same effect upon the potential variations of all three
extremity electrodes if it brings about dilTerences in their spatial relations with
respect to the new bounding surfaces. In experiments of the kind performed by
the investigators just mentioned, a contact or near-contact between one of these
electrodes and the shielding metal screen would bring both to the same or nearly
the same potential. The difference in potential between the screen and the
central terminal would then become equal or nearly equal to the difference in
potential between the latter and the extremity electrode concerned. In other
words, the effect of the asymmetric arrangement of the clectrode.s would be to
make the potential variations of the central terminal with respect to the screen
larger rather than smaller.

Whether bringing one of the extremity electrodes r'erj' close to the screen
would alter the potential of the former, that of the latter, or that of both depends
upon what is considered the proper reference point for the measurement of the
potential of the cardiac field. By connecting the electrode or the screen to earth
the absolute potential of either could be maintained at zero. Since the conduc-
tivity of metal is roughly fifty billion times that of distilled water, the intensity
of the electric forces produced by the heart must be infinitesimal outside the metal
shield, and we agree with Eckey and Frohlich that the potential of the screen
should be considered completely indifferent with respect to the cardiac field-

Differences of opinion on questions of this kind have led to much confusion.
Their source lies in the circumstance that the absolute potential of a given point
on an isolated conductor in which electric currents are flowing is indeterminate
unless the total charge on the conductor is known or the potential of one of its
points has been fi.\ed by grounding it. This difficulty arises because an isolated
conductor may carry a static charge of unknown magnitude. Such a charge over
its surface will raise or lower the absolute potential by the same amount at
every point of the conductor but will have no effect upon the currents flowing
through it. In the case of an infinite conductor this situation cannot arise. If
the conductivity of the isolated conductor under consideration is large enough,
we may think of it as in contact over its whole surface with an infinite conducting
medium possessing a very much smaller conductivity and thus make it possible,
at least theoretically, to choose infinity as our reference point for the measurement
of the field.

The electrical field associated with the heartbeat presents some additional
complications because it varies with time. We have been treating it as though,
at any given instant, it had the' same characteristics that it would have if it were
not changing. Let us suppose, therefore, that there is a static charge on the body
(or any conductoi of which it is a part) which varies in magnitude from instant
to instant, and tha,t the inductive effects of this varying charge mav be neglected.
The potential variations produced by it will then be of the same' magnitude at
every point of the conductor and will have no effect upon the cardiac currents.

WILSON ET AL. :

einthoven’s triangle, unipolar leads, ecg . 291

Potential variations of this sort are imposed upon the cardiac field by selecting
some arl^itrary point on the body and grounding it, or what amounts in effect to
the same thing, making it the reference point for the measurement of the potential.
It is obvious that if the potential of any chosen point was not constant before,
and is constant after it has been grounded, this procedure must either impose
upon every other point of the conductor variations in potential of the same abso-
lute magnitude as those abolished, or alter the distribution of the cardiac currents.
Connecting the body to earth does not have an effect of the latter kind* large
enough to be detected by the electrocardiograph.

If one investigator places his reference electrode on a freshly injured spot
on the ventricular surface and connects it to earth, he will arrive at the conclusion
that, all ventricular complexes represent a combination of tAvo monophasic re-
sponses. Another who places his reference electrode on an uninjured part of the
ventricular surface will not find this view attractive. In leads from all parts
of the body surface each will record large complexes that are practicallj'^ identical
in form, and both will disagree with a third investigator who has placed his refer-
ence electrode as far from the heart as possible and believes that the magnitude
of the potential variations produced by the heartbeat diminishes rapidly as the
distance from the heart increases. As to the variations in the difference in
potential between two specified points on the body surface, all will come to the
same conclusion only if they compare them directly by leading from one to the
other, for neither of the first two investigators will be able to estimate these
potential differences by comparing leads from each of the two points to his refer-
ence electrode unless he makes use of a measuring machine. It is clear that the
arbitrary choice of a reference point for the measurement of the cardiac field
in terms of the potential, and also a purely empirical approach to the selection
of the most useful bipolar leads, is likely to yield a harvest of confusion rather
than enlightenment. We can, of course, give up the concept of the potential and
think of the field of the heart in its vector form; that is to say, as a distribution
of electric currents. Unfortunately, vector fields, in which three numbers must
be associated with every point, are much more difficult to visualize and to analyze
than scalar fields.

Three-dimensional fields of any kind, vector or scalar, are difficult to visualize
unless they have some degree of symmetry. In the case of a field that has this
property, it is profitable to fix the attention upon the point, line, or plane with
respect to which the symmetry subsists. There is nothing to be gained by choos-
ing a reference point for the measurement of the potential in such a way as to give
the measured cardiac field a less symmetrical aspect than that which it has when
expressed as a system of current lines and isopotential surfaces. If this is to be
avoided the potential of the reference electrode should be the same as that of the
point or points with respect to which the cardiac field is most nearly symmetrical;

♦It ^voulcl seem tliat in this case the fluctuating charge on the liody. is represented in- a flow of charce
Into and out of a condenser of, which the plates are the body and the earth. Both the canaeitv Xf t hic
condenser and the resistance in series ’nath it are small, so that the. time constant of the circuit invnivXfi
must bo very short, and tlic static charge involved very small. There is no chance thXt iho
tion of the amount of electricity r^uired to change the potential of the body with reforeUe to the rartli
by a few millivolts could be detected by any, instrument used to take elcctrocardiogm^ms ^ earth

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belter still, if it were possible, the same as that of points far enough from tlie
heart to be beyond an appreciable influence of this field. In the latter case the
potential would be zero where the intensity of the field was negligible. The poten-
tial of the central terminal is the mean of the potentials of the apices of Einthoven’s
triangle and these are nearly as far from the heart as any other points on the
trunk. If the field of the heart, so far as its least intense parts are concerned,
may be regarded as nearly equivalent to that of a dipole located within the heart,
the potential of this terminal is also that of the center of the' dipole, the point
about which the cardiac field is most nearly symmetric, provided that the electric
forces perpendicular to the plane of the limb leads have no significant effect upon
the mean potential of the extremities.

If the potential variations of the reference electrode are large, the ventricular
complexes of all leads from regions where the cardiac field is considerably weaker
and therefore varies less will be very much alike in form. The occurrence of
strikingly similar complexes in leads from points that are widely distributed over
the body and differ greatly in respect to .distance and direction from the heart
is a clear indication that the reference electrode is far from indifferent. If the
cardiac field at points far from the heart is nearly equivalent to that of a doublet,
leads from two points equidistant from this organ and at opposite ends of a line
which passes through its center should yield complexes exactly opposite in
character if the leads employed are unipolar. The average potential over a
spherical surface, due to charges within it, is zero if the net charge is zero-^ as
in the case of dipoles. It seems probable, therefore, that the average of the
cardiac potential* over the body surface must have a small value. If the reference
electrode is indifferent and complexes of one kind are obtained from all parts of a
region close to the heart, such as the precordium, complexes of the opposite type
should be obtained from a still larger diametrically opposite region, such as the
back, which is farther away from the heart. So far as we are able to judge from
our experience with the central terminal, its potential is ordinarily close to the
average of that of the body surface.

In concluding this discussion we may emphasize the fact that all of the
available data which have a bearing upon the questions at issue are consistent.
This is a very important consideration in estimating their significance. The
cadaver experiments indicate that in spite of the irregular shape of the body and
the somewhat eccentric position of the heart it is possible to ascertain the orien-
tation of the frontal projection of the heart’s electrical axis with considerable
accuracy bj' Einthoven’s method. All the immersion experiments that have been
carried out gave substantially the same results. In the case of normal subjects
the potential of the central terminal with respect to an electrode which bore
essentially the same relation to all or nearly all parts of the body surface was
slightly negative throughout the greater part of the QRS interval and did not vary
through a range of more than 0.3 millivolts. The chief question that arises in
connection with these experiments concerns the relative magnitude of the poten-
tial variations of the central terminal before immersion with respect to its potential

the cardiac sources and sinks under the boundary
conditions imposed upon the field to which they give rise

WILSC)N ET AL. ; EINTHOVEN’s TRIANGLE, UNIPOLAR LEADS, ECG . 293

variations after immersion. Due allowance has been made for the short-circuit-
ing effect of the water on the basis previously indicated. That other factors, such
as large variations in skin resistance from point to point, which might alter the :
magnitude of the potential variations in question when the subject was immersed
could have had substantially the same effect in all the experiments performed
seems very improbable. The observ'ations on the difference in potential between ■
the central terminal of the Einthoven triangle and that of the Arrighi triangle
suggests that that the small negative potential of the former observed in the
immersion experiments was due to the effect of electric forces having an antero-
posterior direction. It is desirable to knoAV the magnitude of the error involved
in, determining the inclination of the sagittal projection of the heart’s electrical
axis by Arrighi’s method. This organ is closer to the anterior wall of the chest
than to any other part of the body surface and its position with respect to his .
triangle is not precisely the same as its position with respect to the triangle of
Einthoven.

' /

THE INTERPRETATION OF THE PRECORDIAL ELECTROCARDIOGRAM

A comprehensive article^® on this subject has recently been published from
this laboratory. We propose here to supplement and not to repeat what was
said in that article. W’e shall confine our remarks to a few examples of types of
precordial electrocardiograms that have not been adequately discussed.

Incomplete Right Bundle Branch Block . — ^The electrocardiogram reproduced in
Fig. 4 is that of an obese boy, aged 9 years, who had a speech defect and displayed
evidence of general hypoplasia and mental retardation. The heart was not en-
larged, no significant murmurs were heard, and the blood pressure was 96/40.
There was no history of cyanosis at birth and none was present at the time of the
examination. The limb leads show rather pronounced left axis deviation, a QRS
interval which measui'es approximately 0.09 second, and both an R and an R'
wave in Lead III. Double R waves are also present in precordial leads Vi,
V 2 , and Vb. We believe that many precordial electrocardiograms of this kind
represent incomplete right bundle branch block. We have encountered them
frequently in all types of heart disease and also in many instances in which there
was no other evidence of heart disease. Our interpretation of these curves is
based on fhe occurrence of ventricular complexes of the same form in an electro- ■
cardiogram which was discussed in the article previously referred to (see Figs. ,
14 and 15 of that paper^®). In that instance they alternated with complexes
characteristic of complete right branch block, and the initial phases of the two
types of comple.xes were identical in all leads. The difficulty is that one often
sees an embryonic secondary R, that is to say, a conspicuous notch on the ascend- '
ing limb of S, or a small terminal R' deflection in Lead Vi in cages in which there
is not only no other evidence of heart disease but no increase in the QRS interval
and no trace of a simiDr deflection in Lead V 2 or Lead \^b-‘ The diagnosis of
incomplete right bundle; branch block must,- therefore, be made with caution.
We think that this diagnosis is more likely to be correct when the secondary R

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AMERICAN HEART JOURNAL

wave is conspicuous and is present in Lead as well as in Lead Vi and the QRS
interval measures at least 0.10 second in the limb leads. This diagnosis should
not be made unless the R' deflection rapidly decreases in size as the exploring
electrode is moved toward the left side of the precordium as it invariably does
in complete right branch block. In some cases Lead Vi displays an unusually
prominent R deflection with a prominent notch or slur on its ascending limb, and
if the exploring electrode is moved farther to the right a broad bifid R or a final
R' deflection is recorded. This situation is illustrated in Fig. 5, in which is repro-
duced the electrocardiogram of a boy, aged 17 years, who had a very loud, rasping

Fig. 4. — ^Incompleto riglit bundle brancli block.

systolic murmur accompanied by a thrill in the pulmonic area. He was not blue
at birth but a cardiac abnormality was noted a year later. There was no cyanosis
and roentgenographic examination of the heart was negative. The position of the
electrical axis, the small size of the R wave in Lead Vc and in the leads from the
left back (V7 and Vg), and its large size in the leads from the right side of the
precordium suggest right ventricular hypertrophy. However, this abnormality,
which was suspected on clinical grounds also, does not satisfactorily explain the
occurrence of secondary R waves in the leads from the right side of the chest.

Occasionally, we have seen precordial electrocardiograms which had all the
characteristics of those that are diagnostic of complete right bundle branch block

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except that the QRfe interval did not exceed 0.10 second. Most, if not all, of
these have been obtained in cases in which there were clinical reasons for suppos-
ing that the right ventricle was carrying an abnormally heavy burden. We are
inclined to believe that such tracings represent the combined effect of right ventri-
cular hypertrophy and incomplete right branch block, possibly resulting from the
high pressures sustained by this chamber.

Incomplete Left Bundle Branch Block . — ^This condition is still inore difficult
to diagnose with confidence than incomplete right branch block. It is probable
that it often gives rise to electrocardiograms that are indistinguishable from those
considered characteristic of left ventricular hypertrophy. This opinion is sup-
ported by an observation made by Dr. John B. Levan. He has been kind
enough to send us for teaching purposes the electrocardiogram of a young man
who was able to engage in strenuous exercise and appeared to be healthy in every
respect. Ordinarily, his electrocardiogram was of the normal type but on one
occasion it displayed, off and on, sequential complexes showing pronounced left
axis deviation and deeply inverted T deflections in Lead I. The QRS interval
of these complexes was slightly longer than that of the normal complexes, and
the transitions from the abnormal to the normal mechanism were abrupt. It
is evident that disturbances in intraventricular conduction that behave in this
manner must involve only a single strand of specialized tissue, for it is hardly
likely that several bundles would always cease to function and always recover at
the same instant. Transient incomplete left branch block seems, therefore, to
be the logical diagnosis in this case.

The electrocardiograms reproduced in Fig. 6 are those of a man, aged 49
years, whose blood pressure had been extremely high for a period of at least five
years and who died of congestive cardiac failure in June, 1944. The first tracings,
taken on May 23 of that year, are quite characteristic of complete left bundle
branch block. The QRS interval measures approximately 0.17 second. On May
29, however, the QRS interval had decreased to between 0.09 and 0.10 second
although the QRS deflections of the limb leads still showed conspicuous slurring
and notching. The precordial curves of the same date are similar to those
obtained in many cases of hypertensive heart disease. Note, however, that no
Q wave is present in either Lead Vs or Vs. We have observed the same sequence
of events in a number of other instances. The question arises as to whether the
second set of curves represents incomplete left branch block, some other conduc-
tion defect, left ventricular hypertrophy alone, or a combination of the last two.
If the first is the case, the earliest phases of the QRS complex of the same lead
should have exactly the same outline in both sets of tracings. Unfortunately,
this valuable criterion is often less useful than might be expected. The delay
in the activation of the left ventricle may be nearly as great in incomplete as in
complete left branch block or it may be very slight. If the latter is the case,
the decision must be made on the basis of the form of the QRS complex during the
first 0.01 or 0.02 second of the QRS interval; it will be noted, in the present
instance, that in Leads Vi, V2, V3, and V4 the resemblance between- the earliest
phases of QRS in the two sets of curves is pronounced. In Leads V5 and Vg,

^f9S77

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AMERICAN HEART JOURNAL , .

the R wave begins with a slowly rising portion in the curves of the second set,
but the slope of this initial component appears to be much steeper than, the cor-
responding part of the R wave in those of the first set. About the only thing
that can be said is that if the last set of tracings represents left ventricular,
hypertrophy plus incomplete left branch block, the delay in the activation of the
left ventricle caused by the latter was slight. If a Q wave were present in the
second set of leads from the left side of the precordium, the presence of this
conduction defect could be ruled out with reasonable certainty.

In some cases in which incomplete left branch block is suspected, the pre-
cordial and extremity curves are like those of complete left branch block in every
respect except that the QRS interval is less than 0.12 second.

Fig. 7. — Left ventricular liyportrophy possibly complicated by a defect in
intraventricular conduction.

. Left Ventricular Hypertrophy . — A problem closely related to the one just
_ discussed is presented by the electrocardiogram reproduced in Fig. 7, which is
that of a man, aged 35 years, who had mitral stenosis, aortic regurgitation, and
. pronounced cardiac enlargement. The standard limb leads show conspicuous
left; axis deviation and inversion of the T wave in Leads I and II. The P-R
interval is abnormally long and the QRS interval measures 0.12 second. Because

WILSON ET AL.: EINTHOVEN’s TRIANGLE, UNIPOLAR LEADS, ECG 299; _

of the large voltage of the QRS deflections, the precordial leads were taken with
the electrocardiograph at one-half its normal sensitivity. There is a conspicuous
• Q wave in Lead I and a small Q in Lead Vg. The R wave of the last of these leads
is not broad-topped or bifid, as it usually is in complete left branch block, but '
there is some slurring and notching of the QRS deflections of the limb leads. The ' .
large voltages recorded in Leads Vi, Vo, and V3 strongly support the diagnosis
of left ventricular hypertrophy, but was this condition present alone, in combina-
tion with complete or incomplete left branch block, or in combination with some
other conduction defect? In our opinion, the presence of a Q in Lead I and par- ;
ticularly in Lead Vc plus the absence of a broad-topped or bifid R wave in the
latter make the second possibility very unlikely. It is difficult to decide between
, the other two.

The electrocardiogram reproduced in Fig. 8 is that of a physician, aged 29
years, with mitral stenosis, aortic insufficiency, and pronounced cardiac enlarge-
ment. The limb leads show slight right axis deviation and changes in the P
waves of the type commonly associated with an advanced mitral lesion. The
P-R interval is slightly prolonged and the QRS interval measures appro.ximately
0.105 second. The QRS deflections are slurred. The precordial curves are much .
more like those seen in left ventricular hypertrophy than like those associated with
extreme right ventricular hypertrophy. The voltages of the deflections are
not, however, extremely large and the T waves are normal. This electrocardio-
gram represents either auricular hypertrophy plus left ventricular hypertrophy,
or plus hypertrophy of both ventricles. An increase in the QRS interval is rarely
encountered in the electrocardiograms which are typical of .preponderant right
ventricular hypertrophy.

Pulmonary Embolism . — ^The electrocardiograms shown in Fig. 9 are those of a
woman, aged 39 years, who was subjected to a subtotal hysterectomj'- plus appen- :
dectomy on May 26, 1944. On June 6 it was noted that Homans’ sign was pres-
ent, and on the following day at 8 P. M. the patient had a severe attack of chest
pain accompanied by faintness and dyspnea. The blood pressure fell to 70/50.
The first electrocardiogram was taken at 9:40 p. m. on June 8 and the second was
taken at 4:45 P. m. on June 9. The patient died about five hours later and the.; '
post-mortem examination showed massive pulmonary embolism, pulmonary
. arteriosclerosis with organizing and recanalized thrombi, and some active pul-
monary arteritis. The heart was not grossly abnormal. The two sets of limb. .

; leads are very similar; both show prominent S waves in Lead I and rather con-
■spicuous Q waves in Lead III. The T waves are pointed in Leads II and III
. and there is a sharp bend in the initial limb of the T complex in Leads I
and III. The QRS interval is a little longer in the second set of curves.

The two sets of precordial curves are very different. TheTrst set is notable ■
chiefly for the slight downward RS-T displacement in Leads V3, V.i, and V-
and for the sharp angulation of the ascending limb of T in these leads. The ' -
second set shows late R waves in Leads Vg and Vi and sharply inverted T waves ^ v
in the same leads and is strongly suggestive of incomplete right bundle branch
block. Tt is well known that transient complete right branch block often occurs '

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AMERICAN HEART JOURNAL

in pulmonary embolism and that it is frequently followed by incPmplete right
branch block of gradually decreasing grade. In many cases, a conduction defect
of this sort may account for all of the electrocardiographic abnormalities present.
In the present instance, however, there were changes of the kind that have been
considered characteristic of pulmonary embolism at a time when the precordial
leads showed no evidence of a defect in conduction of the kind in question.

Kig. S — Left ventricular hypertrophy or hypertrophy of both ventricles.

Anterior Injarclion . — ^\Vhen the anterior wall of the left ventricle is infarcted
the resulting changes in the QRS and T complexes are seldom more pronounced
in Lead I than in precordial lead V5. If the anteroseptal wall of the left ventricle
is involved, the diagnostic electrocardiographic signs are usually confined to
one or more of the first four precordial leads and the complexes of the limb leads
are either of the normal type or show modifications of the T waves only. If
the anterolateral wall is involved, diagnostic changes are present in Lead I and
Lead V^, and in some combination of the precordial leads which includes Lead

Pulmonary embolism

302

AMERICAN HEART JOURNAL

V5. There are, however, some striking exceptions to these pneral rules. We
have seen, for example, conspicuous flattening of tlie T waves in Lead I, terminal
inversion of this wave in Lead Vl, and a large pointed positive T wave in Lead III
when the complexes of Leads Vj, Y;, and V3 Avere diagnostic of infarction and those
of Leads \h, V5, and Ve were normal in every respect. More interesting still are
those cases in which the complexes of Lead I are diagnostic or very strongly sug-
gestive of anterior infarction while those of the precordial leads are either of the
normal type or show only minimal changes of the kind characteristic of this lesion.

The electrocardiograms reproduced in Fig. 10 are those of a man, aged 41
years, who gave a historj^ of severe attacks of chest pain in 1943 and developed a
persistent left hemiparesis in hlay of that year. He had been told that his
blood pressure was elevated, but at the time when he was first seen it was only
120/80. The heart was slightly to moderately enlarged ; no murmurs were heard.
There were no signs of congestive cardiac failure. The extremity curves show
conspicuous Q waves and terminal inversion of the T waves in Lead I and Lead
lY- The usual precordial leads are negative except for low R waves preceded b>’
tiny Q waves in Vs and V 4 and terminal inversion of the T waves in V3, \'4, and Ys-
The leads taken from higher levels, particularly those from the 3rd and 4th
intercostal spaces in the left midclavicular and the left anterior axillary line,
show considerably more striking changes. The electrocardiograms of this patient
differ from those attributed to high lateral infarction in a pre\*ious report."'^
The latter showed unusually large R and T waves in the leads from the right side
of the precordium. Such changes suggest posterior rather than anterior infarc-
tion.

Posterior Infarction . — In some cases of posterior infarction in Avhich there
are abnormally large Q waves and sharply inverted T waves in Leads II, III,
and Yp, the same kind of changes are present in Lead Ye. The leads from the
right side of the precordium may, or may not, display unusually large R waves
and tall pointed T waves. Tracings of this kind have been ascribed to infarction
of the posterolateral Avail of the left A'entricle.-^

The electrocardiogram reproduced in Fig. 11 is that of a man, aged 61 years,
who Avas first seen on June 18, 1944. There w’as a history of severe chest pain
which radiated to both arms in NoA'ember, 1943. A diagnosis of coronary throm-
bosis was made at that time and the patient remained in bed for eight Aveeks.
Some dayb before he Avas brought to the hospital he had a second attack of chest
pain folloAAong moderate exertion. A short time after this, tarrj'’ stools Avere noted.
At 4,00 A. M. on June 18 he AA^as aAA'akened by severe pain in the region of the left
scapula, through the chest, and in the left abdomen. When he was examined
some hours later the blood pressure Avas 70/50, the pulse rate AA^as 130 per minute,
and the rectal temperature AA'as 102° F. The heart Avas enlarged, the heart sounds
AA'^ere faint, and no murmurs AA'ere heard. The abdomen Avas somewhat rigid and
tender on the left side. Death occurred at 3:35 P. M. on June 19, shortly after
anot er attack of severe pain in the chest. The location of the infarcted regions
ISC ose > t e post-mortem e.xamination is shoAvn by the sketch reproduced in

WILSON ET AL. :

301

AMP-RirAN 111' Ain JoUKNAi-

Mg. 12. Tlie autojj'iv finding'' incluflnd a pcrfoiatint: ganrrr tiic’('r
by a subplirenic ahscc.sh and fihi inojjiirulnnt pi'iiluniti*-.

I’Ju' elect focardiograin '■liown in big. I.? is tlsa? of ,i man. aged Ah year^,
who had clie*'! pain of short dur.ition on hept. 10, On {Ih> ftjno'.ting day

he had a second attack wliicli lasod one hont. He was tlten kept in bed, and ua*-
Olid that his blood picssure was 200. lb- continned So have {)at!i and ot? Sep-
tember 10 had an nmisuaMy 'toete attack. ,'\t iJu' tinu* of tlie physical e.sainina'
tion on the .satne da}-, he was still lanuplaining t>f p.dn. The idood ptesHurf- 'a .as

150/90 ami the w liite blood count was 1 1,000 per cubic millinieter. The abdntnen
was distended and teiulei. The he.irl was mu unlaipetl, but subsequent roent-
genographic .studies .slunml some bro.-uleriing <<f the not ta. There was a past his-
tory of inlet mil tent claudication, and no pulsation could be fell on palftalion of
the left dorsalis pedis arter\- The patient made a pood recovery from the cor-
onary accident.

The first electrocardiograms taken on September 18 were considered within
normal limits. Thoie was a slight flattening of the T waves in the limb leads and
a slight concavit}' of the KS-T segment in Leads \'i and V;. A number of tracings

WILSON ET AL.: EINTHOVEN’s TRIANGLE, UNIPOLAR LEADS, ECG 305

taken during the next few days were of similar form. On September 27, however,
there was a sharp dip at the end of the T wave in Lead I. The precordial elec-
trocardiogram of the same date shows large pointed upright T waves in Leads V i,
Vo, and Vs in which these waves had previously been small, and terminal inversion
of T in Lead Vq., More striking inversion of T is present in leads from a high
point in the left axilla, from the left posterior axillary line at the level of the
fourth costosternal junction, and from the left scapular region. These findings
suggest that the infarct was on the posterolateral wall of the left ventricle well-
toward the base. This case illustrates the desirability of taking serial electro-
cardiograms when the first tracing is negative and of caution in ruling out infarc-
. tion on the basis of the absence of characteristic electrocardiographic changes.

The electrocardiogram reproduced in Fig. 14 is that of a man, aged 78 .
years, who was awakened at 2:00 A. m. on Sept. 29, 1944, by severe epigastric
pain radiating to the left scapula. The pain was followed by coughing and the
expectoration of frothy blood-tinged sputum. When seen at the hospital some
hours later, he was cyanotic and the blood pressure was 110/76. On previous
examinations the systolic pressure had been in the neighborhood of 150 to 160.
The heart was borderline in size; the sounds were extremely faint; no murmurs
were heard. Coarse moist r51es were audible over the entire lung field. Death
occurred about forty-eight hours after the onset of symptoms.

The limb leads are diagnostic of right bundle branch block, but also show
large Q waves in Leads II and III and upward RS-T displacement in the last of
these leads, which are. characteristic of posterior infarctioh. The precordial leads,
however, in addition to the late R waves in Leads Vi, V 2 , and V e, which are attrib-
utable to right branch block, show pronounced upward RS-T displacement in
these sarrie leads and in Leads V 3 and V 4 as well. These findings suggest antero-

WILSON ET AI-. : EINTHOVEN’s TRIANGLE, UNIPOLAR LEADS; ECG , 307

Fig. 14. — Right bundle branch block associated •\vlth signs of posterior infarction in the limb leads and

signs of anteroseptal infarction in the prccordial leads.

septal infarction. The location of the.infarcted regions disclosed by the post-
mortem examination is shown in Fig. 15. Both coronary arteries showed pro-
nounced atherosclerotic changes and the lumen of the anterior descending branch,
of the left was nearly obliterated. No thrombi were found in these vessels.

FiK. 10. — ChaiiKCs sukkosIUik old posterior Infarction In a caso In which tho clinlc.al history made St seem very iinllUoly that infarction
had occurred. Tho symhol B Is uscmI to dtislRiuito an esophageal lead. The nuntcral attachetl to this loiter elves the distance (In continieters)
of tho c.xplorintt clcctrodo from tho nares.

WILSON ETAL.; EINTHOVEN’s TRIANGLE, UNIPOLAR LEADS, ECG 309

The electrocardiograms reproduced in Fig. 16 are those of a man, aged 39;
years, who had two spontaneous attacks of anginal pain in June, 1944. The first
, pain was felt in the region of the lower sternum and persisted throughout the
day; it was not particularly severe. The second attack occurred about thirty-
six hours later; the pain was under the midstern;um and lasted for about thuty ,
minutes. Subsequently, there was mild anginal pain on brisk exertion. Physical
examination on Sept. 21, 1944, was negative except for a moderately loud late
systolic murmur at the apex. The blood pressure was 128/75. There was noth-
ing in the past history which threw any light on the development of angina pec- :
toris.

The electrocardiogram shows large Q waves in Leads II, III, and Vjp and in
all of the leads from the ventricular levels of the esophagus. There are also
rather prominent Q waves in Lead Ve. Np changes in the T deflections suggesting
myocardial infarction are present, but when such changes are present initially
they may disappear in the course of three or four months. We consider the elec-
trocardiograms in this case characteristic of old posterolateral infarction, but
a diagnosis of infarction could not be made because standard limb leads taken
in 1936 during a physiologic experiment showed exactly the same peculiarities
as those taken at the time of our examination. We do not know what the cor- .
rect explanation of these observations may be. We feel, however, that it is
imperative to avoid making a clinical diagnosis on the basis of electrocardiographic
exanjination when, after adequate investigation, it is certain that this diagnosis
is not supported by the history and other clinical data.

REFERENCES

1. Einthoven, W., Fahr, G., and de Waart, A.: Ueber die Richtung und die manifeste Grosse
der 'Potentialschwankungon im menschlichen Herzen und ueber den Einfluss der Herzlage
auf die Form des Elektrokardiogramms, Arch. f. d. ges. Physiol. 150: 308, 1913.

2. Lewis, T., Drury, A. N., and Iliescu, C. C.: A Demonstration of Circus Movement in Clini-
cal Flutter of the Auricles, Heart 8: 341, 1921.

3. Fahr, G., and Weber, A.; Ueber die Ortsbestimmung der Erregung im Menschlichen
Herzen mit Hilfe der Elektrokardiographie, Deutsches Arch. f. klin. Med. 117: 361, 1914.

4. Wagner, G.: Physikalische Untersuchungen zum Dreieckschema nach Einthoven, Zen-
tralbl. f. Herz-u. Gefasskr. 16; 1, 1924.

, 5. Johnston, F. D., Kossmann, C. E., and Wilson, F. N.: Unpublished obserx^ations.

6. Wilson, F. N., and Herrmann, G. R.: Unpublished observations.

7. Stratton, J. A.: Electromagnetic Theory’, New York, 1941, McGraw-Hill Book Co.

'8. Helmholtz, H.: Ueber einige Gesetze der Vertheilung elektrischer Strome im kOrperlichen
Leitern mit Anwendung auf die thierisch elektrische Versuche, Poggendorff’s Annalen 89: -
211,1853.

9. (a) Wilson, F> N., Macleod, A. G., and Barker, P. S.: Electrocardiographic Leads Which

Record Potential Variations Produced by the Heart Beat at a Single Point, Proc. Soc.
Exper. Biol. & Med. 29; 1006, 1932.

(b) Wilson, F. N., Johnston, F. p., Macleod, A. G., and Barker, P. S.: Electrocardiograms
That Represent the Potential Variations of a Single Electrode, Am. Heart j. 9; 447
1934.

,10. Burger, R., and Wuhrmann, F.: Ueber das elektrische Feld des Herzens. 11, Mitteilunv.

, Cardiologia 3: 139, 1939.

,11. Arrighi, F.: Personal communication, 1942.

12. Arrighi, F.: El Eje Electrico del Corazon en el Espacio, Facultad de Ciencias Medicas
■ Univ. Nacional de Buenos Aires, Buenos Aires, 1938. '

310 AJIERICAN HEART JOUENAL

13. Eckev, P., and FrOhlich, R. ; Zur Frage dcr unipolaren Abicitung dcs Eiektrokardiogramins,
Arcb.'f. Kreislaufforsch. 206: 181, 1938.

14 Burger, R.: Ueber das Elektrische Feld dcs Herzens. 1. Miticilurig, Cardioiogia 56,
1939.

15. Wolferth, C. C., and Livezey, M. M.: .AStudyof the Methodsof Making So-Called Unipolar
Electrocardiograms, Am. Heart J. 27: 764, 1944.

16. Cole, K. S., and Curtis, H. S.: Electric Impedance of Nitclla During Activity, J. Gen.
Physiol. 22: 37, 1938.

17. Lewis, T., and Rothschild, M. A.: The Excitatory Process in the Dog’s Heart. Part H.
The Ventricles, Phil. Tr., Lond. .Series 13 206: 181, 1915.

18. Wilson, F, N., and Herrmann, G. R.: Bundle Branch Block and Arborization Block, Arch.
Int. Med. 24: 153, 1920.

19. Wilson, F. N.; The Distribution of the Potential Differences Produced by the Heart Within
the Body and at Its Surface, Am. Heart J. .S: 599, 1930.

20. Wilson, F. N., Wishart, S. W., and Herrmann, G. R.: Factors Influencing Distribution of
Potential Differences, Produced bv Heart Beat, at Surface of Bodv, Proc. .Soc. Exper. Biol.
& Med. 23: 276, 1926.

21. Macleod, A. G., M'ilson, F. N., and Barker, P. S.: The Form of the Electrocardiogram.
1, Intrinsicoid Deflections in .Animals and Man, Proc. Soc, Exper. Biol. & Med. a: 599,
1930.

22. Wilson, F. N., Macleod, A. G., and Barker, P. S.: The Order of \'entricular Excitation in
Human Bundle Branch Block, A.m. Heart J. 7: 305, 1932.

23. Wilson, F, N., Macleod, A. G., and Barker, P. S. : The Potential \'ariations Produced by
the Heart at the Apices of Einthoven's Triangle, .Am. Heart J. 7: 207, 1931.

24. Kelloge, 0. P. : Foundations of Potential Theorv, New York, 1943, Frederick Ungar Pub-
lishing Co.

25. Wilson, F. N., Johnston, F. D., Rosenbaum, F. F., Erlnnger, H., Kossmnnn, C. E., Hecht,
I-L, Cotrim, N., Menezes de Oliviera, R.. Scarsi, R., and Barker, P. S.: The Precordial
Electrocardiogram, Am. Heart J. 27: 19, 1944.

26. Durant, T., Ginsburg, M. D,, and Roesler, M.: Transient Bundle Bninch Block and Other
Electrocardiographic Changes in Pulmonary Embolism, .Am. Heart J. 17: 423, 1939.

THE EFFECT OF SALICYLATES ON ACUTE
RHEUMATIC FEVER

Lieutenant Colonel Harry A. Warren, M.C., Lieutenant Colonel C. S.:
Higley, M.C., AND Major F. S. Coombs, M.C., Army of

the United States

T he most important problem in the treatment of acute rheumatic fever is
the prevention of organic heart disease. To effect this it is essential that
the rheumatic inflammator^'^ reaction be suppressed in the minimum of time and
that polycyclic attacks of rheumatic fever be prevented. If rheumatic attacks
were always monocyclic and short lived, severe cardiac damage would rarely
occur. For many years salicylates have been used in rheumatic fever in an
attempt to attain these objectives. There is general agreement on the rapid
antipyretic action of salicylate and on the efficient alleviation of pain and swell-
ing of the joints with salicylate therapy. Whether salicylates prevent polycyclic
attacks or reduce the incidence of permanent cardiac damage has been disputed for
years.

In 1914, 'Miller^ reviewed the literature on the action of salicylates in acute
articular rheumatism. He found that with salicylate therapy pain was relieved
in an average of 5.3 days; without salicylates pain persisted for 13.4 da^^s. Re-
lapses occurred in 30.3 per cent of the 1,258 patients receiving salicylates, but
only 6 per cent of the 974 patients who did not receive salicylates had recurrence
of their symptoms. There was no difference in the length of hospital stay in the
two groups. Miller quotes Pribram on the incidence of cardiac complications:
cardiac damage developed in 28.8 per cent of patients on salicylate and in 23.4
per cent of patients not receiving salicylate. During the period reviewed, Miller
states that 15 to 20 grains of sodium salicylate every two or three hours was con-
.sidered a moderate dose and many physicians gave as much as 300 grains a day;
In 1918, Hanzlik, Scott, and Gauchat- in a study of the specific effect of salicylates
on rheumatic fever concluded that while salicjdate is effective it is not specific
and that other drugs will produce the same results though perhaps not so con-
sistently. They stated that salicylate was no more than a symptomatic remedy.
They found no reduction in the occurrence of endocarditis with salicylate therapy.
In 1925, SwifU stated that salicylates had a favorable effect on the exudative
phase of rheumatic fever but that it failed to influence markedly the proliferative'
lesions. He felt that this explained why salicylates had ho effect on chorea
and did not prevent valvular lesions in patients receiving full dosage. He did
erriphasize that these drugs were of great assistance in reducing the fever and cori-

Prcsented in part before the Eighteenth Annual Meeting of the Central Societv for Clinical Re-
search, Chicago, 111., Nov. 2 and 3, 194.5. * . . ,

. Received for publication Jan. 31, 1946.

311

312

AMERICAN HEART- JOURNAL

trolling the “toxic state.” The tendency to lose weight was less marked in
patients receiving salicylates. With the reduction in fever and toxicity there
was a lowering of the heart rate’. Swift pointed out that if salicylate eliminated
the edema from the valves, as it does from the periarticular tissues, some of the
traumatic injury to the endocardium might -be eliminated. He emphasized the
importance, both to the physician and the patient, of continued care, even after
all symptoms are relieved by salicylate therapy, as otherwise the patient may in
the end suffer more permanent injury than if he were untreated. In 1933,
Graef, Parent, Zitron, and Wyckoff"* reported a series of 105 cases of acute rheu-
matic fever treated only with opiates and local therapy to the affected joints.
They stressed the tendency of the acute manifestations of rheumatic fever to
subside spontaneously and often rapidly.

In 1943, Coburn® reopened the problem of salicylate therapy in rheumatic
fever in his report of 101 cases treated with varjdng amounts of sodium salicylate.
Sixty- three patients received only small doses of the drug, and 21 developed
organic heart disease. Thirty-eight received 10 Cm. or more of sodium salicjdate
daily, and none of these developed heart disease. Coburn administered sodium
salicylate by mouth and also intraA'^enously in doses of 10 to 20 Cm. daily. He
felt that by giving the medication by vein, a more rapid and sustained rise in the
plasma concentration of the drug was obtained. His studies were controlled by
estimations of the plasma level. He concluded that a plasma salicylate level of
at least 35 mg. per 100 c.c. may be required to suppress the rheumatic reaction
and that plasma levels below 20 mg. per 100 c.c. maj'’ be sufficient to relieve symp-
toms while masking a progressive inflammatorj'^ process.*

Hanzlik® credits Mendel with the first use of intravenous salicjdate in
1904. Hanzlik® quotes Matta, Lesne, Gilbert, Couty, and Bernard as using this
method of administration. These clinicians claimed certain advantages in the
intravenous method over the oral route: namely, the avoidance of gastric dis-
turbances, emesis, and side reactions in general; more rapid absorption of the
drug; and finalty the prevention of cardiac complications. Coburn has revived
the interest in this method and claims that a more rapid elevation of the blood
salicylate is obtained and that the patient is more quickly brought under control.

McEachern' has reported his results in 350 cases of acute rheumatic fever
treated between November, 1943, and June, 1944. Toxic reactions were frequent
with intravenous medication and minimal in the orally treated group. Cardiac
sequelae were present in both groups. He concluded that oral administration
of 10 to 16 Cm. of sodium salicjdate was the most satisfactory method of treat-
ment. laran and Jacobs® concluded that intravenous salicylate offered no ad-
vantages in treatment and that the technical difficulties and annoying symptoms
outweighed the possible benefits of a more rapid rise in the plasma salicylate level.

Hanzlik,® Goodman and Gilman,® and, more recently, P. K. Smith*® have
concluded that intravenous administration is unwarranted because of the rapid
and almost complete absorption of sodium salicylate from the gastrointestinal
tract. Smith has shown that peak plasma levels are reached about one hour after

f Coburn introduced the term (7am??ia per cubic centimeter for salicylate levels. AVo feel that such
tcrmuiologj' may be confusing and prefer to retain the more familiar milligram per 100 c.c. for the sake

WARREN ET AL. : SALICYLATES AND ACUTE RHEUMATIC FEVER 313

oral administration. Hanzlik states that the advantages claimed by the sup-,
porters of the intravenous method are unsupported by any evidence and that,
when administered iii this way, salicylate may cause considerable damage to the
heart and other important organs.

In June, 1945, Keith and Ross^^ reported their results in the treatment of
two groups of patients with acute rheurnatic fever in the Royal Canadian Nav 5 L
The sedimentation rate returned to normal in an average of four weeks in a group
of 70 patients receiving 10 to 13.3 Gm. of salicylate per day and in four and one-half
weeks in 33 patients receiving 0 to 1.7 Gm. a day. Three patients in the low
dosage group and five in the high salicylate dosage group developed heart disease.
Five patients who had pre-existing heart disease showed progression, two in the
low and three in the high salicylate group. They could not conclude that large
amounts of salicylates were of any more benefit than small doses. Taran and
Jacobs® recently reported their experience with large doses of salicylate. They
concluded that large doses of salicylate brought about prompt and effective re-
sponse both in patients with polyarthritis without carditis and in those patients
with carditis. They state that if therapy is not instituted promptly activity" con-
tinues for many weeks. Small doses of salicylate in their experience had no
more effect than no salicylate at all in patients with carditis. Murph}-,^-
in a recent report of careful studies in twelve patients receiving large doses of
salicylate, questions the usually accepted view that salicylates promote the sub-
sidence of rheumatic joint inflammation. In several patients characteristic ,
lesions developed in a variety of sites during the course of hea\'yr salicylate therapy.
It is obvious that there is still no agreement as to the efficiency of salicylate in
preventing cardiac damage or the ability of large doses to reduce rheumatic ac-
tivity more quickly than small amounts.

METHODS OF STUDY

We have observed 186 cases of acute rheumatic fever in young adults
between November, 1942, and September, 1945. These patients have been
observed under three different therapeutic regimes. Some have been treated
with small doses of salicylate given only to relieve symptoms. Others received
large doses by mouth until all evidence of rheumatic activity had subsided. A
third group received sodium salicylate intravenously for one week and then large
oral doses. We wish to report our experience with these three types of treat-
ment considering the effect on the length of rheumatic activity, on polycyclic
attacks, on pericarditis, and on the occurrence of permanent cardiac damage.

, The diagnosis in each case was carefully determined and in all cases the
criteria established by Jones'® were applied. In each case, before therapy
was started, a complete history was taken and a physical examination was made;
other studies made on each patient included an electrocardiogram, an ''x-ray
of the heart, hemoglobin determination, erythrocyte count, leucocyte and differ-
ential counts, urine examination, and erythrocyte sedimentation rate. A,
twenty-four hour period of observation was used in most cases before starting
therapy and in a few cases three days to two weeks of observation took place

314

AMERICAN HEART JOURNAL

before the diagnosis was accepted and therapj' was started. Routine urine e.v-
aminations were done once weekly. Certain patients with acute rheumatic
fever were not included in this study, because of the occurrence of purulent com-
plications Avhich would influence the sedimentation rate and fever. The patients
with pneumonitis are included e.xcept where sputum e.xamination and the clinical
course indicated that it was not of rheumatic origin. In all cases studied from
November, 1943, on, sedimentation rates were done two or three times weekly
for two to four weeks and then once weekly; electrocardiograms were taken
two or three times weekly for two weeks and then once weekly. The patients
studied in 1942 and 1943 received these tests less often. In 1942 and 1943 the
Wintrobe method ivas used in determining the sedimentation rate, but after
JanuarjL 1944, the Westergren method was used, without correction for the cell
volume. This was not necessary as no significant anemias were encountered.
Hemoglobin, red blood cell counts, and leucocyte counts were done twice monthly.
In many of the later cases antistreptolysin determinations were done to assist in
establishing a diagnosis. All but two of the patients were men. The age range
was 18 to 40 years; 70 per cent were under 25 years and 87 per cent were under
30 years of age. There were no significant differences in the age composition of
the three treatment groups. Fifty-one per cent of tliose receiving small doses
and 39 per cent of those receiving large doses had a history of previous rheumatic
fever. Pre-existing rheumatic valvular heart disease was present in 12.5 per
cent of the small dose group and in 5 per cent of the large dose group. The
differences in these proportions are not statistically significant.

Eighty-eight patients were treated with small doses, ranging from 2 to 7 Gm.
a day. The drug was given until nausea or tinnitus developed or until relief of
symptoms was obtained, and the dose Avas reduced markedly or it was eliminated
entirely when the pain and fever had subsided, regardless of the level of the sedi-
mentation rate. Sodium bicarbonate was usually given in equal doses. The
medication Avas giA^en four to eight times during the day from 8. ’00 A. M. to 10:00
P. M. In some cases acetyl salicylic acid AA'^as used and in others sodium salicylate.
Sixty-four patients treated by this method AA’^ere admitted during the Avinter of
1942-1943, 17 in the Avinter of 1943-1944, and 7 in 1944-1945.

Fifty patients Avere treated AAuth 10 to 16 Gm. of sodium salicylate per day
by mouth. The medication AA'^as divided into equal doses and giA'^en at four-hour
intervals throughout the tAA^enty-four hours. Sodium bicarbonate AA'^as giA'^en
Avhen necessary to reduce gastric irritation and to prevent toxic reactions. Plasma
salicylate determinations Avere done several times Aveekly and the dosage AA'as
adjusted to maintain lev^els of 35 to 45 mg. per 100 cubic centimeters. The
salicylate AA'^as continued in this dosage until the sedimentation rate had main-
tained a normal level for at least tAvo Aveeks. If the sedimentation rate rose after
salicylate AA’-as stopped, the drug AA’^as again given in the same dosage until the
sedimentation rate again remained normal for tAA’’0 Aveeks. In some cases salicy-
late Avas omitted for several days because of a high plasma level or because of
toxic symptoms.

WARREN ET AL. : SALICYI^ATES. AND A.CUTE RHEUMATIC FEVER : , 315

Forty-eight patients were given 10 Gm, of sodium salicylate in 1,000 c.c.
of normal saline daily for seven days. . The infusion was administered slowly
over a six to eight-hour period. In several cases doses of 14 and 20 Gm. were
given for one or several days because of continued symptoms. The day following
the last intravenous injection these patients were started on 10 to 16 Gm. of;
sodium salicylate by mouth daily and continued as in the large oral dosage
group. . Plasma salicylate levels were determined several times weekty in this
group. The patients treated with large doses of sodium salicylate were observed
from March, 1944, through the remainder of the study.

THE EFFECT ON THE SEDIMENTATION RATE

The erythrocyte ‘sedimentation rate, while a nonspecific test, has been
accepted as a sensitive indicator of rheumatic activity. Most authorities agree
that physical activity should be limited until the sedimentation rate has reached
a normal level. The comparative effects of the three methods of treatment on
the sedimentation rate should be indicative of the relative effect on rheumatic
activity.

The sedimentation rate may show wide fluctuations in acute rheumatic
fever as the inflammatory process varies in intensity. A certain number, those
with monocyclic attacks, will show a prompt drop in the rate to a normal level
(Fig. 1, Patient H. P.), If these patients are used to show the effect of salicylate
therapy it will indicate a marked effect. Some patients may show an apparent
response but then continue with lower but abnormal sedimentation rates suggest-,
ing a repression of rheumatic activity by salicylate (Fig. 1, Patient A. E.). Other,
patients will have polycyclic attacks with recurring waves of activity. Here,
if salicylate is given with the rate elevated, it will show an effect as the rate falls;
If it is then omitted the rise in rate suggests that salicylate was stopped too
quickly. However, in Fig. 2, Patient A. D., it is seen that this may occur
regardless of salicylate therapy with so-called adequate blood levels. Some
patients show continuous rheumatic activity with wide fluctuations of the
sedimentation rate uninfluenced by adequate plasma salicylate levels (Fig. 2,
Patient R. N.). Graef, Parent, Zitron, and Wyckoff^ have stressed these varia-
tions in duration of activity and the tendency of acute manifestations to subside
spontaneously in the course of untreated rheumatic fever. Ernstene^'^ found
that frequently the sedimentation rate increased slightly after stopping salicylate
and then dropped promptly to the previous level.

In order to take into consideration these fluctuations in rheumatic activity
and the effect of salicylate therapy on the disease, we have added the days in
which the sedimentation rate was above 20 mm. per hour to obtain the total days
elevation for each case. An average number of days of elevated sedimentation
rate was then determined for each treatment schedule. These averages have been
subjected to, statistical analysis to determine the significance of the differences
under the three plans of treatment.

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Fig. 1. — Patients A. E. and H. P. Tlie chart shows the relationship of the erythrocyte sedimentation
rate, plasma salicylate levels, and the dose of sodium salicylate by mouth.

In an effort to separate the severe cases from those with mild rheumatic
inflammation, we have divided the cases into two groups; those with sedimentation
rates of 60 mm. per hour or less and those with higher rates.

One hundred twenty-six cases were observed where the highest sedimentation
rate was over 60 mm. per hour. Table I shows the average mlmber of days of
elevated sedimentation rates in the three treatment groups. There is a range
of ten days between the large oral dosage and the intravenous groups with the
small dose group falling between the two. Statistically, the difference of these
means is not significant and we can conclude that in these three groups there
was no more rapid reduction of rheumatic activity with large than with small
amounts of salicylate.

Sixty cases were studied where the highest sedimentation rate was under 61
mm. per hour. Fifty-one patients received small doses of salicylate and had
elevated sedimentation rates for an average of 35.2 days. There were only four

WARREN ET AL. ; SALICYLATES AND ACUTE RHEUMATIC FEVER

Fig. 2. — Patients R. N. and A. D. The chart shows the relationship of the erythrocyte sedimentation
rates, plasma salicylate levels, and the dose of sodium salicylate intravenously and by mouth.

Table I. The Effect of Salicylate on the Erythrocyte Sedimentation Rate

MEAN DAYS
ELEVATED
E. S. R.

E. S. R* over 60 fum.lhour

Small oral . .
Large oral . .
Intravenous.

E. S. R. ii7ider 60 vun.Pwnr

Small oral 51 *35.2

Large oral 5 36

Intravenous.; 4 27.8

AU Cases

Small oral 88 45.1

Large oral ,50 49.8

Intravenous 48 58.6

Total large and oral and intravenous 98 , 54. 1

*E. S. R.=erythrocyte sedimentation rate.

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patients who received intravenous therapy and five who received large oral doses
in this group, too few to offer any accurate comparison in effectiveness of therapy
(Table I).

Table I also shows the consolidated data for all cases observed, both high
and low sedimentation rate groups. Here the greatest difference between the
means is 13.5 days, between the small dose and the intravenous therapy group.
Here again, by statistical analj'sis there is no significant difference between the
average days of elevated sedimentation rate for the three treatment groups.
If we consider all the large dosage patients, both oral and intravenous, the
average number of days of elevated sedimentation rate is 54.1. The difference
between this average and that for the small dose group is nine days, again not a
statistically significant difference. The median for the small dose group was just
over six' weeks while the median for the large dosage group was also six weeks.

100

80

I I SMALL DOSE
m LARGE DOSE

60

n

40

ao

WEEKS 10 20 30

Elg. 3. — The percentage of cases wth elevated sedimentation rates, by weeks, under treatment

with small and with large doses of salicylate.

The higher average days resulted from seven patients with sedimentation rates
which remained elevated for more than twenty-two weeks. Fig. 3 shows the
proportion of the total small and large dose groups with elevated sedimentation
rates in consecutive weeks of observation. Here it can be seen that actually
there is no real difference. The two curves follow each other almost e.xactly ex-
cept for those cases with prolonged activity which perhaps by chance occurred
only in the last two seasons and were treated with large doses. In any event
from our data it is seen that large doses of salicylate are no more effective than
small doses in reducing an elevated sedimentation rate.

THE EFFECT ON FEVER

The data on the effect on the temperature are based on oral temperature as
recorded by the ward nurses in a routine manner. Temperatures were taken four
times daily during the period of acute illness and then twice daily, at 8 ;00 A. M.
and 4:00 P. M. One hundred seventy-one patients showed a temperature of

WARREN ET ,AL; : SALICYLATES AND ACUTE RHEUMATIC FEVER , 319

Table II. The Effect of Salicylate on the Number of Days of Fever

CASES

MEAN DAYS
. OF.FEVER

Small oral

82

11.63

Lar^e oral

44

3.-77

Intravenous

45

• ‘4.57 ■■

Total large, oral and intravenous

89

4.16 "

99.2° F. or more on at least one occasion. Table II shows the average number of
days of fever in the three treatment groups. The greatest difference is 7.8
days between the small and the large oral treatment groups. Between the intra-
venous and the small therapy group is a difference of seven days. By statistical
analysis both of these differences are significant, and we can conclude that
large doses of salicylate will reduce the temperature to normal more quickly
than small doses. It is also evident that oral, large dose therapy is more effec-
tive than the intravenous method. Fig. 4 shows the proportion of the small and
total large dose (both oral and intravenous) groups with fever in consecutive
^ days of observation. Here again, the advantage of using large doses of salicylate
in eliminating the febrile reaction is evident.

Fig. 4. — The percentage of cases -svith fever, by days, under treatment ■with small and

large doses of salicylate.

THE EFFECT ON POLYCYCLIC ATTACKS .

Coburn® has pointed out the difficulty in determining whether any form
of treatment has a therapeutic effect in rheumatic fever. About 20 per .cent of
:young adults may be expected to have monocyclic attacks and recover spontane-
ously in about three weeks with symptomatic therapy. We have tabulated the
data on polycyclic attacks in our group and included every patient who showed a

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Table III. The Effect of Salicylate on Polycyclic Rheumatic Fetch

POLYCYCLIC

TOT.4L CASES

CASES

. %

E. S. R. over 60 inm.jhoiir

Small oral

37

19

51.3

Large oral

45

28

62.1

Intravenous

44

28

63.6

E. S. R. under 60 mm. /hour

.Small oral

51

16

31.2

Large oral

5

2

Intravenous

4

2

All Cases

Small oral

88

35

30

Large oral

50

Intravenous

48

30

Total large, oral and intravenous

98

60

secondarj'^ elevation in sedimentation rate after the rate had reached a normal level
(Table III). In some patients there were, in addition, clinical signs and symp-
toms indicating rheumatic activity. Thirty-five patients, 39.8 per cent of all
those receiving small doses, showed such polycyclic manifestations. Thirty
patients, 60 per cent of all patients receiving large oral doses, and 30 patients,
62.5 per cent of all receiving intravenous therapy, showed polycyclic attacks.
The difference of these means is statistically significant. In our experience
large dose therapy does not reduce the occurrence of polycyclic attacks. It is
interesting to note that Miller,^ in his review in 1914, found a similar effect with
salicjdate therapy. Of the patients of his series receiving salicylate, 30.3 per
cent had relapses while only 6 per cent of those not receiving the drug suffered
such poU'cyclic attacks.

the effect on valvular heart disease

The most important factor in determining the efficacy of various types of
therapy is the prevention of valvular heart disease. This is a difficult problem
to evaluate in a short study such as this. To be certain one should re-examine
these patients several years after the attack of rheumatic fever. The problem
of the evaluation of a systolic apical murmur is an important aspect of this
question. Wlien a patient is admitted to the hospital with an aortic diastolic

WARREN ET AL. : SALICYLATES AND ACUTE RHEUMATIC FEVER - 321 .

or mitral systolic murmur it is frequently impossible to say how long these
murmurs have been present. As a rule, it can be assumed that the murmurs were
present before. Furthermore, it is difficult to tell whether the present attack
has produced additional cardiac damage or not. We have used Levine’s’^
method of grading systolic murmurs throughout this study. Levine states that .
several observers will vary no more than one grade in classifying murmurs under
this system so that a variation of two grades indicates an actual change. For
example, a progression from a Grade 1 to a Grade 3 systolic murmur is evidence
of actual change in volume of the murmur and, unless associated with elevation of
temperature and tachycardia, can be interpreted as evidence of an organic change.
Increase in cardiac size under observation is another evidence of increased cardiac
du.mage.

Due to the limited period of observation, any data on the development of
cardiac damage we now have are obviously incomplete. However, we, can
answer the question of the development of cardiac damage with Coburn’s large
dose method. Fourteen patients in the entire series developed evidence of or-
ganic heart disease or showed increased damage of pre-existing heart disease .
(Table IV).

Table IV. The Effect of Salicylate on the Develop.ment of Valvular Heart Disease

SMALL DOSE

LARGE DOSE

i

Anrfir. insnffir.iencv

2 cases

1 case

3 cases

2 cases

2 cases

1 3 cases

i

IV'Tifrfll fif:<>nosis

PrnViahIp mitral insiiffiripnr.v

There were seven patients who developed new cardiac murmurs or showed
evidence of increased damage of pre-existing heart disease while receiving large
doses of salicylate. Five were given large doses by mouth and two received intra-
venous therapy. Five of these men had a past history of rheumatic fever. There
were two patients who developed aortic insufficiency, one with a past history
of rheumatic fever and one without such a history. One received intravenous
therapy and one oral. There is no question but that these two men developed
valvular heart disease while receiving large doses of salicylate. Two patients
receiving large oral doses developed mitral stenosis under observation where no
presystolic murmur had been heard on admission. Both patients, however,
had a past history of rheumatic fever. The remaining three men were admitted
with no cardiac murmurs. They developed persisent Grade 2 apical systolic
murmurs. All three gave a past history suggesting previous rheumatic fever.

There were also seven men receiving small doses of salicylates who developed
organic heart disease or showed signs of increased damage of an old lesion.
Here again two patients developed aortic insufficiency, neither man having a
past history of rheumatic fever. One patient developed a presystolic apical
murmur and showed an increase in the intensity of a pre-existing apical systolic

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murmur. Two patients developed persistent Grade 2 apical systolic murmurs
where none existed on admission. Only one of these men had a past history of
rheumatic fever. The sixth man on admission had a soft Grade 1 apical sj^stolic
murmur which progressed to a rough Grade 3 murmur by the time of discharge.
The seventh patient was admitted with mitral stenosis and insufficiency and
auricular fibrillation of long standing. He had a mild attack of rheumatic
lever but tliere was possible further cardiac enlargement as the transverse
cardiac diameter by x-ray examination increased one centimeter. All of the.se
patients had received small amounts of salicjdate but had remained on limited
physical activity until the sedimentation rate had remained at a normal level for
at least several weeks.

We can conclude, then, that large doses of salicylate will not prevent the
occurrence of valvular heart disease or the progression of pre-existing cardiac
damage. In our experience there was the same incidence of heart disease in the
two groups under observation. Because of the short period of observation, we
are not in a position to state that either one or the other method of therapy
will lessen cardiac damage.

THE EFFECT ON PERICARDITIS

It is probable that large amounts of salicjdate will relieve the joint pain
and discomfort more quicklj^ than small doses. We ha^'e no statistical data on
this aspect of the problem but in using large doses we had little or no difficulty
in relieving the symptoms within one to three days. A more certain test of
this is the effect on acute pericarditis. There were three cases with acute peri-
carditis treated by intravenous therapy and one treated with large oral doses of
salicylate. Three occurred in the winter of 1944 and one occurred in 1945.
The longest period of ele\'ated sedimentation rate was thirtj'-three days; the
average was twenty-six days. The longest period of fever was six days; the
average was four. One of these patients developed aortic insufficiency. How-
ever, the effect of large dose salicylate therapy was striking. There was rapid
subsidence of all joint and chest pain and fever. This was in marked contrast to
the cases of pericarditis of the previous season which were treated with small
doses of salicylate. Two of these four patients received sulfadiazine because of
the presence of pneumonitis and pericarditis and the possibility of a bacterial
infection. One of the two also received penicillin for thirty-si.v hours. In each
case there was no effect from the antibiotics but a prompt response to salicjdate.

In the fall and winter of 1942-1943, we had seven cases of acute pericarditis
treated vith small doses of salicylate. The average period of ele'vation of the
sedimentation rate in this group was forty-four days with a range of fifteen to
seventy-seven da\s. Fever was maintained for as long as thirty-four daj's in
one case, the average was twenty-one days. Several of these box's were acutely
ill for seveial v'eeks. Two of the seven are not included in the averages given
• because of the development of complications which would influence sedimentation
rate and fever. One died in cardiac failure; this was our only death from acute
rheumatic fever Post-mortem e.xamination showed complete obliteration of

WARREN ET AL.: SALICYLATES AND ACUTE RHEUMATIC FEVER 323

the . pericardial cavity, multiple areas of pulmonary infarction, and thrombo-
phlebitis of the prostatic venous plexus. ' The second patient developed an acute
empyema during the course of his rheumatic fever, which necessitated thor-
acotomy and prolonged drainage.

It would appear from our experience that the use of large amounts of
salicylate will relieve the symptoms and cause more rapid subsidence of acute
pericarditis than will small doses. This in itself would be a definite factor in
support of large doses. However, Ave had only four patients treated with large
doses. Moreover, the two groups did not occur in the same season, and it is
well known that rheumatic fever varies in severity from one season to another.
Despite these criticisms, we have been impressed with the prompt control of peri-
carditis with large dose therapy.

THE EFFECT ON THE P-R INTERVAL

The occurrence of a prolonged P-R interval in the electrocardiogram is
accepted as the most frequent and important electrocardiographic manifestation
of acute rheumatic fever. The effect on this sign of cardiac involvement would
be helpful in evaluating the efficiency of salicylate therapy. Wyckoff, DeGraff,
and Parent’® have reported careful studies on this problem in eight patients
receiving salicylate and ten receiving no therapy. They found that the P-R
interval showed wide and inconstant variation uninfluenced by salicylate in
doses of 8 Gm. per day. For accurate appraisal of this phase of the problem
electrocardiograms should be taken daily. Many of the patients studied in 1943
did not have frequent electrocardiograms. In some cases three weeks elapsed
between tracings. However, by presenting our data by weeks some information,
can be deduced. A total of 47 patients showed a prolonged P-R interval of
over 0.22 seconds, or A-V dissociation. Seventeen patients receiving small doses
of salicylate showed prolonged P-R intervals and 52.9 per cent of them showed a
normal P-R interval by the end of two weeks. However, many of these patients
did not have electrocardiograms at intervals close enough to allow accurate
evaluation. Five of the patients receiving small doses, whose tracings were taken
frequently, required an average of ten days for the P-R interval to reach normal.
Eighty per cent had a normal P-R interval at the end of one week. In 81.2 per
cent of those receiving large oral doses and in 78.5 per cent of those receiving intra-
venous therapy the P-R intervals had returned to normal at the end of two weeks.
While our data are not sufficient to conclude unequivocally that small doses are
as efficacious or more so than large doses, they suggest certainly that there is no
apparent advantage in intravenous therapy over large oral medication in the
effect on the P-R interval changes.

DISCUSSION

There is no danger in giving such large doses if the signs of toxicity are
known and carefully appraised. Tinnitus and diminished hearing are practi-
cally universal with 10 Gm. of sodium salicylate daily and are of no practical
significance as far as toxic reactions are concerned. Severe toxic reactions

324

AMERICAN HEART JOURNAL

are marked by hj^perpnea, tetany -with carpopedal spasm, and progression to
maniacal delirium and loss of consciousness. They present a serious situation
in the advanced state. Pustular acne is not uncommon with the to.xic reaction
and is frequently troublesome. It promptly subsides on stopping the drug.
The serious toxic reactions in our experience are always preceded by hyperpnea.
In this stage reduction of the dose of salicylate or the use of sodium bicarbonate
soon relieves the symptoms by reducing the plasma level of the drug. If the
drug is continued in the same dosage without sodium bicarbonate, hyperpnea
increases and delirium appears. In this stage the use of intravenous saline is
necessary to return the body chemistry to normal and relieve the symptoms.
We^^ have shown that the chemical changes consist of a rcspiratorj'^ alkalosis
with resultant water retention and diminished renal function. It is essential
that the premonitory symptoms of severe toxic reactions be well known by those
using these large doses of salicylates. In our series of young adults, 20 to 25
grains of sodium salicylate every four hours (six times daily) were usually suffi-
cient to maintain plasma levels of 35 to 50 mg. per 100 cubic centimeters. No
sodium bicarbonate was given with this dose and toxic reactions were rarelv
experienced.

The use of intravenous salicylate is open to considerable question. We
were able to maintain more satisfactory plasma lev^els with oral administration.
P. K. SmitlP® has shown that with oral administration the plasma level reaches
a peak in one hour. It would appear that intravenous therapy is not necessary.
In those patients with heart failure or impending failure, the use of intravenous
saline maj!- well be dangerous and may increase the degree of failure. None of our
patients receiving intravenous therapy was in cardiac failure and there were no
serious reactions. However, nausea and vomiting are very common with intra-
venous salicylate and in some cases we were forced to discontinue this method of
administration because of constant vomiting. After a few hours these patients
were able to resume salicylate therapy in large oral doses without difficulty.
In our experience intravenous therapy offers no advantage over oral therapy in the
control of these patients.

In our group of young adults, the administration of large doses of sodium
salicylate was more efficacious than small doses: first, in reducing the febrile
response ; and, second, in the treatment of acute pericarditis. It did not diminish
the period of rheumatic activity as shoAvn by the effect on the sedimentation rate;
it did not prevent the occurrence of valvular heart disease; and it did not pre-
vent the progression of polycyclic attacks of rheumatic fever. There may be cer-
tain advantages in using large amounts especially at the start of therapy and until
the fever and the symptoms have subsided. There seems to be some question
as to the necessity for continuing the salicylate after these effects have been
achieved. Patients taking large doses have almost constant tinnitus and dimin-
ished hearing so that cessation of the drug will make them more comfortable.

It would appear that the use of large amounts of salicylate offers some ad-
vantage in the treatment of rheumatic fever. The early reduction of fever
and pain would tend to decrease the heart rate and reduce cardiac work. How-

WARREN ET AL. : SALICYLATES AND ACUTE RHEUifATiC FEVER 325

r. - , ’

ever, it will not prevent cardiac damage as is shown by the experience of Me- ■
Eachern,’^ Keith and Ross,^^ and ourselves. Moreover, as Swift^ has pointed out,
if in attaining this early relief of symptoms the patient is led to believe he is cured .
and is allowed to resume normal activity, he may suffer as much or more per-
manent injurj' than if he were untreated. It is important to emphasize that .
sodium salicylate in these doses does not bring about a cure. There is still no
chemotherapeutic routine which will obviate the needier prolonged reduction in
physical activity as the most important method of treatment in acute rheumatic
fever.

CONCLUSIONS

1. The use of sodium salicylate in amounts of 10 to 16 Gm. per day will
reduce the temperature more quickly in acute rheumatic fever than will small
doses. Likewise large doses appear to offer an advantage in the treatment of
acute rheumatic pericarditis.

2. The use of sodium salicylate in doses of 10 to 16 Gm. per day will not
prevent the development of cardiac damage or the progression of pre-existing ,
heart disease. Large doses of salicylate will not serve to shorten the period of
rheumatic activity anymore than small amounts. Large doses of salicylate will
not prevent the development of polycyclic attacks of rheumatic fever.

3. The routine use of sodium salicylate by intravenous infusion is not war-
ranted by the evidence presented to obtain a rapid elevation of the plasma
salicylate level, to maintain a high plasma level, or to effect the fever or sedimen-
tation rate.

4. If large amounts of salicylate are given, either orally or intravenously,
the premonitory signs of toxicity must be recognized early and the dose must be
reduced to prevent progression of the symptoms.

5. It appears that the use of large amounts of salicylate may offer some
advantage in the first weeks of therapy and may bring about a rapid reduction
of the fever and alleviation of the symptoms; but the continued administration
of large amounts of this drug until the sedimentation rate is normal is of ques-
tionable value.

REFERENCES

1 Miller, J. Li: The Specific Action of Salicylates in Articular Rheumatism, J. A. M. A. 63; '
1107-1109, 1914.

2. Hanzlik, P. J., Scott, R. W., and Gauchat, P. C.: The Salicylates. X. The Specificity
of Salicylate in Rheumatic Fever, J. Lab. & Clin. Med. 4: 112-122, 1918.

3. . Swift, H. F.; Rheumatic Fever, Am. J. M. Sc. 170; 631-647, 1925.

4. Graef, I., Parent, S., Zitron, W., and Wyckoff, J.; Studies in Rheumatic Fever. 1. The
Natural Course of Acute Manifestations of Rheumatic Fever Uninfluenced by Specific
Therapy, Am. J. M. Sc. 183; 197-210, 1933.

5. Coburn, A. F.; Salicylate Therapy in Rheumatic Fever, Bull. Johns Hospkins Hosp. 73;
435-464, 1943.

6. Hanzlik, P. J.: Actions and Uses of Salicylates and Cinchopen in Medicine, Medicine 5;

. 197-374, 1926.

7. McEachern, G. C.: Use of Oral and Intravenous Salicylate in Acute Rheumatic Fever,

New's. Letter, AAF Rheumatic Fever Control Program 2: 1-8, 1945. Published by Josiah
Macy, Jr., Foundation, New York, N. Y. - .

8. Taran, L. M., and Jacobs, M. H.; Salicylate Therapy in Rheumatic Fever in Children,

. J. Pediat. 27; 59-68, 1945.

326

AMEKfCAN HEART JOURNAL

9. Goodman, L., and Gilman, A.: The PliarniaroloRical Pasis of Therapeutics, New York,
1941, The Macmillan Co,, p. 231.

10. Smith, P. Iv.: Salicylate Metabolism in Normal SubjccI, News Letter, AAF Rheumatic
Fever Control Program 2: 8-11, 194.S. Published by Josiah Macy, Jr. Foundation, New
York, N. Y.

11. Keith, J, D., and Ross, A.: Observations on .Salicylate 7'hcrapy in Rheumatic Fever, Canad.
M. A. J. 52: 5.54-559, 1945.

12. Murph}^, G. E.: Salicylate and Rheumatic Activity, Hull. Johns Hopkins IIosp. 77: 1-42,
1945.

13. Jones, T. D.: The Diagnosis of Rheumatic Fever, J. A. M. A. 126 : 481-484, 1944.

14. Ernestene, A. C.; Er\'throcyte Sedimentation, Plasma Filjrinogen and Leucocytosis as
Indices of Rheumatic Infection, .\m. J. M. Sc. IRO: 12-24, 1930.

15. Levine, S. A.: Clinical Heart Disease, ed. 2, Philadelphia, 1942, \V. U. .Saunders Co., p. 272.

16. Wyckoff, J., DeGrafT, A. C., and Parent, S.: The Relationship of .Auriculo-Yentricular
Conduction Time in Rheumatic Fc\-er to Salicylate Therapy', .Am. Hlakt J. .5: 568-574, 1930.

17. Coombs, F. S., W’arren, H A., and IHglcv, C. S.: Toxiritv of Salicylates, J. Lab. & Clin.
Med. 80: .378-379, 1045.

A REFRACTORY CASE OF SUBACUTE BACTERIAL ENDOCARDITIS .
DUE TO VEILLONELLA GAZOGENES CLINICALLY ARRESTED.

-BY A COMBINATION OF PENICILLIN, SODIUM PARA-
AMI NOH I PPURATE, AND HEPARIN

Leo Loewe, M.D., Philip Rosenblatt, M.D., and Erna Alture-
Werber, Ph.D., Brooklyn, N. Y.

OINCE the value of penicillin alone or with heparin has been established,^""’
^ bacterial endocarditis is being studied very intensively. It is not surprising,
therefore, that infecting organisms of abizarre nature are occasionally encountered.
A most unique example of a bizarre infecting organism was found in a patient
who was admitted to the Jewish Hospital of Brooklyn on April 14, 1944. Before-
the patient entered our hospital, the organism had been recovered from the blood
stream with great difficulty, under the direction of Dr. Gregory Schwartzman, arid
identified by him and his group as a Veillonella species. This same gram-negative
anaerobic coccus was isolated by us repeatedly and its biologic characteristics,
including its response in the test tube to various anti-infective agents, were studied,
in great detail. It was considered worth while to report this case (1) because of
the unusual nature of the infecting organism, its extreme resistance to penicillin
presenting an almost insurmountable obstacle to the successful treatment of the
patient, and (2) because of the singular measures employed in overcoming all the
difficulties encountered and accomplishing clinical arrest of the infection. , The
case is further noteworthy because of the huge amounts of penicillin* which
were employed, a fact which gives further testimony to the nontoxicity of this
agent. Finally, it is the first recorded instance, so far as we know, wherein sodium
para-aminohippuratef was used as an indispensable enhancing agent in the actual
treatment of a patient infected with a refractory organism.

case report

S. Z., a 35-year-old white man, was admitted to the Jewish Hospital of
Brooklyn on April 14, 1944, with a history of fever of seven months’ duration.
The patient’s illness began on Sept. 4, 1943, with chills, fever, and pain in the right
shoulder. At this time a painless, red spot appeared on the big toe of his right
foot. He was admitted to another hospital where a course of atabrine was given
without effect. One month later he was transferred to a second hospital where .

From the Department of ^letlicine and the Department of Laboratories, Jewsh Hospital of.
Brooklyn..

Aided by a grant from the John L. Smith Research Fund of the Jewish Hospital of .Brooklyn.

Received for publication Feb. 13, iQiG. ‘ ,

*We are indebted to Mr. John L. Smith of the Chas. Pfizer & Co., Inc,, for the generous supplies
of a specially prepared solution of penicillin utilized in these studies.

tWe are indebted tn Sharp and Dohmc, Inc., for the liberal supplies of .sodium para-aminohippurate
and to Dr. Karl H. Beyer of that organization for his ad\’ice and cooperation.

,327

328

AMERICAN HEART JOURNAL

he was treated with massive doses of the sulfonamide drugs. Al the latter institu-
tion a gram-negative anaerobic organism was isolated from the blood stream
which was identified as VdlloncUa species. There was some symptomatic im-
provement as a result of the chemotherapy, but, as soon as treatment was
stopped, the clinical sjmiptoms recurred. The patient denied having had
rheumatic fever.

On admission to our institution, the patient was found to be of athletic
habitus. His temperature was 100.4° F., pulse rate, 100; respirations, 24;
and blood pressure, 105/65. The heart did not appear to be enlarged, but there
was a loud, rough, apical systolic murmur. The spleen was slightly tender and
palpable 2 fingerbreadths below the costal margin. 'Fhere were two red spot.s
on the right thumb. Culture of tlie blood on admission was sterile. The sedi-
mentation rate was 92 mm. in one hour (Westergren method); hemoglobin, 78
per cent; red blood cells, 4,200,000 per milliliter; white blood cells, 7,100 per
milliliter, with 70 per cent polymorphonuclear leucocyie.s, 26 per cent lymph-
ocytes, and 4 per cent monocytes.

Treatment was begun on April 18, 1944, witli penicillin and heparin. The
patient was given a two-week course of penicillin and heparin bj* continuous
intravenous drip, totalling 3,430,000 units of penicillin and 900 mg. of heparin.
Therapy had to be interrupted on one occasion because of \'iolent pyrogenic reac-
tions in which the temperature readied a height of 107° F.

During treatment, the patient ran a daily remittent temperature up to
104° F. which apparentlj' was uninfluenced by the treatment. On May 5 he
was given sulfadiazine in dosages up to 9 Gm. daily. This was continued for a
period of ten days and was supplemented with 20,000 units of penicillin every two
hours intramuscularly during the last four days of this cycle. Again, little or
no success attended this treatment e.\cept for the fact that the temperature con-
tinued at a slightlj’’ lower level. Sulfonamides were therefore discontinued, and
the patient was again put on continuous intravenous penicillin therap}’^ receiving
240,000 units daily for six days with no clinical benefit. Penicillin was discon-
tinued on May 19, 1944, and oral sulfadiazine was again resumed. On May 24,
the oral chemotherapy was supplemented with intravenously admijiistered sul-
fadiazine; 20 Gm. of the sodium salt, combined with 30 Gm. of urea, in 1,000 ml.
of normal saline was administered daily. This was continued until May 31
and was of no benefit to the patient. On June 1, he was again put on continuous
intravenous penicillin, receiving 500,000 units daily. This had to be discontinued
after four days because of limited supplies. On June 7, massive intravenous
sulfadiazine was again started. He received 20 Gm. of the drug combined with
30 Gm. of urea and 1 Gm. of ascorbic acid in 1,000 ml. of normal saline; but because
of the mutilated condition of the patient’s veins, therapy had to be su.spended
the following day. The patient received no therapy at all during the next week
and the temperature unaccountably declined gradually and reached normal
on June 14. On this date, for the first time since admission, culture of the
blood yielded a gram-negative anaerobic organism, Vcillonella species. The
organism was thereafter repeatedly recovered from the blood stream until the

LOEWE ET AL. : SUBACUTE BACTERIAL ENDOCARDITIS . 329

infection was apparently arrested. On June 21, the patient was again started
on massive cyclic intravenous sulfonamide therapy. He was given 20 Gm.
of sulfadiazine plus 30 Gm. of urea and 1 Gm. of ascorbic acid dissolved in 1
liter of distilled water on two successive days each w'eek for the next four weeks.
The patient’s condition, however, did not improve, and consequently penicillin-
heparin was again started on July 14. A fourteen-day course of treatment was
given, with daily dosage of one million units of penicillin plus 100 mg. of heparin
in 1 liter of solute. Although the temperature curve remained relatively flat
during treatment, as soon as it was suspended, the daily, swinging character, with
spikes up to 103° F.,' was resumed (Fig. 1). A blood culture taken during treat-
ment was negative, but one repeated the day treatment was stopped was positive.

DAY OF

1LLNESS36 42 49 56

-1- POSITIVE BLOOD CULTURE

1 — Granli slio'iving typical claUy fluctuations in temperature wliile patient was clinically and

bacteriologicaily active.

The patient’s veins were in such poor condition that it was necessary to defer
penicillin therapy until August 9, when it was again administered under the same
dosage plan. Treatment was continued for nine days, when available veins gave
out. During this span of treatment the temperature continued its remittent
course, but the daily peaks were on a lower level, i.e., up to 101° F.

In view of the ineffectiveness of treatment up to this point, all therapy
was now interrupted and the patient was investigated for possible extracardiac
foci of infection. Several devitalized teeth were found and these, were surgically
removed on Sept. 19, 1944. The patient Avithstood the procedure Avell, but his
clinical course indicated continued bacterial activity. A blood culture taken on
September 25 was again positive.

Up to tliis date, the patient had been in the hospital for about five and one-
half months and had received a total of almost 31 million units of penicillin.
Although the endocarditis remained active, his general status was surprisingly
good. It Avas felt that, if nothing else, treatment had succeeded in maintaining
a status quo and that, ultimately, persistence and reAused dosage schedules AAmuld
meet wnth success. , .

330

AMERICAN HEART JOURNAL

Between September 25 and October 30 the patient was given another course
of penicillin. The basic dosage plan was now 2 million units dailj-. During por-
tions of this course the diluent used was 1,000 ml. of sodium para-aminohippurate
in 4 to 8 per cent concentration. Treatment under this plan was entirely
probatory and had to be interrupted on several occasions because of compli-
cating local thrombophlebitic reactions. In all, he received 45 million units of
penicillin, but, at the end of this span, the temperature curve reflected clinical
activity although blood cultures were sterile.

On November 6, an eighteen-day course of treatment was begun. The
treatment plan at this time called for 2 million units of penicillin daily dissolved
in 1,000 ml. of 4 per cent sodium para-aminohippuric acid. When treatment was
discontinued on November 24, there had been absolutely no change in the tem-
perature curve. A blood culture taken on November 28 was positive. About
the most that could be said at this juncture was that there still had been no de-
terioration in the patient’s general condition.

Obviously, with so much intravenous work having been done, the patient’s
veins were seriously compromised. It was therefore necessary to defer further
therapy until December 11. At this time the daily dosage plan for penicillin
was revised to 5 million units, and, in order to conserve the veins, it was dissolved
in 500 ml. normal saline and given by continuous intramuscular drip. Treat-
ment by this route proved e.xtremely painful and distressing and had to be sus-
pended four days later, after a total of 20 million units had been administered.

Continuous intravenous medication was again resumed on December 19;
the daily dosage plan at this time varied from 2 to 5 million units of penicillin
plus 200 mg. of heparin dissolved in 1,000 ml. of normal saline. At times, the
diluent used was 8 per cent sodium para-aminohippurate so that blood assays
for penicillin with and without the supplemental use of this drug could be done.
Treatment was continued for thirty-one days and was stopped on Jan. 19, 1945;
a total of 131 million units of penicillin had been given. During much of this
course, the temperature receded and remained flat. This was most encouraging
in view of the fact that blood cultures were also negative. However, on January-
24, the patient had a chill and the temperature again began its daily remittent
course with peaks up to 103° F.

As a result of the encouraging response observed during the previous span
of treatment, another course was projected with increasing dosage of penicillin
up to 10 million units daily, combined with heparin. The basal daily dosage for
a good portion of this period was 5 million units. Treatment was begun on
January 31, and continued for thirty-seven da^'^s, ending on March 8, 1945;
a total of 173 million units of penicillin were given. The general condition of the
patient remained in statu quo during this treatment. The temperature curve
became irregularly lower and the 'cycle was finally interrupted because of the
apparent futility of the treatment program and the fact that the patient’s veins
again were badly mutilated.

Probationary in vitro tests had indicated the eflPectiveness of streptomycin.
Pending the acquisition of adequate amounts of this antibiotic and in order to

LOEWE ET AL. : SUBACUTE BACTERIAL ENDOCARDITIS - 331.

allow both the patient’s morale and his veins to recover, he was sent home and
given a respite from hospital routine.

Up to this .time, the patient had been in the hospital almost a full year and
had received a total of about 467 million units of penicillin. Despite the fact that
his endocarditis was clinically and bacteriologically still active, his general condi-
tion was quite favorable. There had been no embolic complications.

During the month the patient was at home the organism was again subjected -
to intensive study. It was finally identified as Veillo7tella gazogeyies. Inasmuch
as there was unexpected delay in obtaining streptomycin, the organism was
retested against penicillin. In vitro tests showed bacteriostasis at 10 units of
penicillin per milliliter. However, 30 units of penicillin per milliliter were re-
quired for a complete bactericidal effect. It was apparent that the previous
dosage schedules had been inadequate, since blood assays had never reached ap-
propriate therapeutic levels. Since our studies® had shown that we could expect
serum penicillin levels of approximately 1 unit per milliliter for each million
units of penicillin administered daily, it Avas obvious that the requisite dosage
schedule called for at least 30 million units per day. While it was theoretically
possible to administer this huge daily dosage of penicillin it was felt that further
experimentation with the use of para-aminohippuric acid as an enhancing agent ; ,
was indicated. These experiments (Tables I and II) were accordingly carried
out during the first few weeks following the patient’s readmission to the hospital
on April 9, 1945.

On his return to the hospital, it was evident that the patient's general
condition had not deteriorated. He was febrile and two blood cultures taken on
April 5 (at home) and April 10 revealed numerous colonies of Veillonella gazo-
ge 7 zes. Probatory e.xperiments Avith various dosage schedules of penicillin
together AAoth para-aminohippuric acid (Table II) led us to assume that adequate
therapeutic levels could be consistently maintained if the folloAAung program AA^as
folloAA^ed; (1) minimum daily dosages of 10 million units of penicillin, (2) minimum
daily dosage of 240 Gm. of sodium para-aminohippurate.

The patient wms accordingly started on his neAV treatment program on May
11, 1945. He AA^as given, daily, 10 million units of penicillin dissolved in 2 liters
of 12 per cent sodium para-aminohippuric acid solution to AA^hich AA'ere added
50 mg. of heparin. This modest amount of heparin, by preventing regional
thrombophlebitis, has been found effective generally in the face of huge penicillin
dosage. Over a period of sixteen days (Figs. 2 and 3), he received the equivalent
of thirteen full days of treatment, or 130 million units of penicillin. The results
AA'Cre prompt and dramatic. Within three days after the program AAas initiated,
the temperature became normal and has remained so far almost six months. Asa
prophylactic measure, the remainder of his potentially infected teeth AA^ere surgi-
cally removed. The patient Avas discharged from the hospital on June 23, 1945,
clinically AA’ell.

At the time of discharge the patient AA^eighed 190 pounds (86 kg.) as contrasted
AAuth.a loAA' of 166 pounds (75 kg.) on April 10, 1945. The spleen, AA'hich had pre-
viously been consistently palpable, receded promptly. The sedimentation rate

332

AMERICAN HEART JOURNAL

was 12 mm. in one hour as compared with a high of 95 mm. on May 5, 1944.
The blood picture showed hemoglobin, 90 per cent; red blood cells, 4,660,000;
white blood cells, 6,850, with a differential of 55 per cent polymorphonuclear

DAY OF

ILLNESS 367 377 387 397 407 417

iiJ

(X

D

tr

LlI

a.

5

bJ

H

Rrrftffl

a= 5,000,000 UNITS PENICILLIN + 120 GM.SODIUM
FARA-AMIN0HIPPURATE+50MGM HEPARIN

+ = POSITIVE BLOOD CULTURE
NEGATIVE BLOOD CULTURE

Elg. 2. — Graph showing resi)onso of patient to curative cycle of therapy.

PENICILLIN UNITS/ML OF SERUM

MGMj y. P.A.H.A. IN BLOOD

Rig. 3. Graph showing actual blood assays of penicillin and para-aminoliippuric acid

during curative cycle of therapy.

leucocytes, 44 per cent lymphocytes, and 1 per cent eosinophiles. Previously,
t ere had been a peristent secondary anemia which was controlled only by
repeated transfusions of whole blood. The albumin and erythrocytes found in

LOEWEETAL.: SUBACUTE BACTERIAL ENDOCAKDITIS 333

the urine during the active phases of the disease disappeared with termination
of the infection. The patient has been seen at intervals since his discharge. His
condition is excellent, and cultures of the blood have been consistently sterile.

EXPERIMENTAL STUDIES

Blood cultures were taken in 0.1 per cent brain-heart infusion agar broth
(Difco) and 0.1 per cent Savita glucose agar broth, to both of which was added
0.1 per cent agar. The cultures were incubated for four to seven ways at 37° G.
and then surface plated on blood agar by inoculating the plates with the incubated
blood broth culture. The transplanted cultures were placed in a candle jar
(10 per cent carbon dioxide) and kept for three days at 37° C. Colonies were-
picked from these plates, transferred, and identified. After repeated transfers,
the use of a candle jar could be dispensed with and the organism could be grown
sluggishly at room temperature. The organism was identified as Veillonella-
gazogenes^ which, according to Bergey,*^ is prevalent in the saliva of man and other
animals. Although it was not possible to isolate the organism from the patient's
mouth or from his tooth sockets and roots, the portal of entry may nevertheless
well have been the oral cavity.

As indicated in the clinical review, the organism, was extremely resistant to
daily dosages of penicillin per se up to and including 10 million units. In vitro
titrations of suspensions of the organism against varying concentrations of peni-
cillin showed bacteriostasis at 10 units of penicillin per milliliter. A complete
bactericidal effect was not obtained until the concentration of 30 units of penicillin
per milliliter was reached. Although streptomycin was not available for clinical
use, it was possible to obtain some for in vitro experimental purposes. It was
found that the inhibiting concentration of streptomycin was 10 units per milliliter.

It was necessary to evaluate dosage schedules of the chemotherapeutic
agents in the light of these facts. Previous studies® had indicated that with a
given dosage schedule of penicillin administered by the continuous intravenous
route, expected sustained serum assays approached 0.1 unit per 100,000 units
daily. In other words, in order to attain bactericidal serum penicillin levels in
this patient, the daily dosage theoretically would have had to be at least 30
million units.

Because variations in blood levels exist in the individual case, an experiment
was designed to see what levels could be obtained in this patient with varying
dosages of penicillin. Equivalent dosages of penicillin were calculated and dis^
solved in 166 ml. of normal saline to cover an experimental period of two hours
for each dose. The patient was carefully observed throughout so that the pre-
scribed amounts of penicillin were infused. Blood was drawn at the end of each
hour and serum penicillin assays were performed according to the method of
Rosenblatt, Alture-Werber, Kashdan, and Loewe.' Table I indicates the
serum penicillin levels obtained with equivalent daily dosages up to 30 million
units per day.

334

AMERICAN HEART JOURNAL

Tahlc I. Scrum Penicillin Levels Wnii Varying Dos\gl or Penicillin

PENICILLIN*

unhs/hr.
(X 1.000)

EQUIVALENI

DAILY

DOS VGE

(X 1,000)

SERUM PENICILLIN

units/ml.

1 HOUR

2 HOURS

AYERAC.E

THroRETICAL+

DEVIATION

415

9,960

3 33

12 0

7 67

9 96

- 2 29

457 5

10,980

8 57

8 57

8 57

10 98

- 2 41

500

12,000

15 0

12 0

13 5

12 0

A- I 5

.541 5

12,966

15 0

15 0

15 0

12 9

-r- 2 1

582 5

13,980

7 5

15 0

11 25

13 98

- 2 74

625

15,000

15 0

15 0

15 0

15 0

0 0

667 . 5

16,020

24 0

15 0

19 5

16 0

3 5

Total - 7 44

+ 7 1

710

17.040

20 0

20 0

20 0

17 0

+ 30

750

18,000

12.0

15 0

13.5

18 0

— 4 5

792 5

19,020

15 0

30 0

22 5

19 0

+ 3 5

835

20,040

30 0

24 0

27 0

20 0

+ 70

875

21.000

15 0

30 0

22 5

21 0

+ 1.5

918

22,020

30 0

30 0

10 0

22 0

+ 80

960

23,010

30 0

30 0

30 0

23 0

+ 70

1,000

24,000

17 1

20 0

18 56

24 0 1

- 5 44

1,042 5

25,020

24 0

30 0

27 0

25 0

- 2 0

1,085

26.040

30 0

40 0 '

35 0

26 0

+ 90

1,127 5

27,060

30 0

»

30 0

27 0 ;

+ 30

1,170

28,080

15 0

20 0

17 5

28 0

- 9 5

1.210

29,100

48 0

40 0 '

44 0

29 1 !

"i" 14- 9

1,260

30,220

60 0

40 0

50 0

39 2

+ 10 8

>

1

'.Total -21 44

!

1

1

+67 7

*Djlupnt vas 83 ml of Tiormal saline per liour Till'! Is caiihTiloiit lo nppiovitnatelj 1.(100 nil. per
tThls is liasocl upon expected serum ponlcUHu level of 0 1 unit per dally dosaso of 100 000 units

It is seen that with dosages up to 15 million units jier day the actual figures
obtained were fairly close lo theoretically expected values. W ith dosages above
15 million units daily, most of the actual serum assays tended to be higher than
the theoretical. This may possibly be due to the fact that the point of maximal
renal clearance for penicillin had been exceeded. This problem, however, is being
further investigated.

According to this stud^c daily dosage of 20 million units of penicillin or more
might consistently yield the requisite bactericidal level of 30 units per milliliter of
serum. It was felt that a saving of penicillin could be effected through the
concurrent use of sodium para-arm'nohippurate, which Beyer and his co-workers*'’

had proposed as an agent for aiding the economy with which the body utilizes
penicillin.

Our previously published studies® confirmed Beyer’s observations, but it
was found necessary to administer at least 200 Gm. of sodium para-aminohip-
puiate daily in order to attain blood concentrations sufficient to augment
serum penicillin levels appreciably. In order to administer this amount of the

LOEWE ET AL. ; SUBACUTE BACTERIAL ENDOCARDITIS 335 -

Table It. Augmentation of Serum Penicillin Levels by Simultaneous Administration

OF Para- Aminohippuric Acid

HR.

i

> *

1 penicillin’^

. untts/hr.

equivalent
[ daily

DOSAGE

SODIUM

PARA-AM 1 NQHI PP U rate!

1 blood serum 1

PENICILLIN

units/ml.

ASSAY -
P. A. H.J

.mg.%

.1

1 417,500

1 10,020,000

0

i

7.5

2

i ■

1

i

1 j

0

7.5

3

i i

fl2 percent Sodium P.A.H.

15.0 !

39.7

4

1 i

land priming doses of 50

15.0

27.6

3

[

Ic.c. 20 per cent solution

15,0 1

59.6

6

lat three and five hours

15.0

47.5

"7

0

15.0 i

24.2 .

8.

t

i

1

0

15.0

10.2

1

625,000

15,000,000

0

12.0

^ 2

0

13.2

3

(12 per cent Sodium P.A.H.

20.0

34.1

4

1 and priming doses of 50

30.0

35.0

]c.c. 20 per cent solution'

30.0

51.8

' 6 i

lat three and five hours

30.0

60.5

. :7. :

0 i

30.0

26.6 •

■ ';8 .

0

30.0

12.3

' T J

832,500

19,980,000

0

15.0

2

0

15.0

—

3

12 percent Sodium P.A.H.

30.0

29.4

4

and priming doses of 50

40.0

32.8

■ 5

* c.c. 20 per cent solution !

40.0

61.3

6

at three and five hours ^

48.0

60.5

7

0

48.0 i

31.5

8

1

i 1

0

40.0

12.9

^Durinc control run of two hours (see text), the diluent for penicillin was 160 ml. of normal saline.
This is enuivalont to a daily intravenous of approximately 2.0)0 milliliters.

tOurinp .sodium para-aminoliippurate run of four hours the diluent for pemcillin was 333 ml. of
12 per cent sodium para-arainohippurate in distilled water. This is equivalent to 2 liters daily, or 240
Gih of the drug. The actual amount given during the four-hour period was 48 grams.
tP. A. H.=Sodium para-arainohippurate.

enhancing agent effectually, the total daily volume of fluid given intravenously
had to be increased from 1 to 2 liters, since a 20 per cent concentration of sodium
para-aminohippurate was found to be too irritating for continuous venoclysis.
A 12 per cent concentraton of the drug (120 Gm. per liter) was satisfactory for
rriaintenance purposes.

Table II summarizes an experiment designed to test the enhancing effect of
para-aminohippuric acid. Study of the table shows consistent augmentation of
the serum penicillin levels by the simultaneous administration of sodium para-
aminohippurate. Although the short-term experiment indicated that a minimum
daily dosage of 15 million units of penicillin together with para-aminohippurate
might be required for optimum results, it was felt that under actual clinical condi-
tions, there might be a cumulative effect of the antibiotic with smaller dosage.
It was decided, therefore, that the projected therapeutic course should encompass
the simultaneous, continuous administration of 10' million units of penicillin daily'
dissolved in 2 liters of 12 per cent sodium para-aminohippurate in distilled water..
Heparin was added in order to maintain a continuous intravenous flow and make
possible an uninterrupted span of treatment.

336

AMERICAN HEART JOURNAL

Fig. 3 indicates the actual serum penicillin and para-aminohippuric acid
levels obtained during this span of treatment. The determinations were taken
usually at the end of a day’s run, prior to attaching a fresh bottle of soluton.
It is observed that most of the^peniciliin levels are within or above the desired
effective therapeutic zone. The fact that this course of treatment resulted in the
apparent clinical arrest of the disease process is confirmation of the validity of the
experimental approach.

As a corollary to what has been presented, it was necessary to ascertain
the effect, if any, of sodium para-aminohippurate upon the infecting organism.
Titrations were therefore carried out in brain-heart infusion broth, and the
results are summarized in Table III.

Table III. Table Showing Resistance of Veilloneli.a Gazogenes to Therapeutic Agents

drug

BACTERIOSTASIS

MINIMUM LETHAL DOSE

Penicillin

Penicillin plus P. A. H.,* 20 nig.%..
Penicillin plus P. A. H., .30 mg.%. .
Penicillin plus P. A. H., 40 nig.%..
Penicillin plus P. A. H., 50 nig.%.. .

P. A. H

P. A. H. plus penicillin, 10 units/nil.
Streptomycin

10 O.Kforcl units per milliliter
10 O.xford units per milliliter
10 O.xford units per milliliter
10 Oxford units per milliliter
10 Oxford units per milliliter
40 mg. per cent

16 mg. per cent

10 units per milliliter

30 Oxford units per milliliter
30 Oxford units per milliliter
26 Oxford units per milliliter
20 O.xford units per milliliter
15 O.xford units per milliliter
163 mg. per cent

63 mg. per cent

10 units per milliliter

“■P. A. H.=Soclium paru-aminohippuratc.

It was noted that sodium para-aminohippurate itself is bacteriostatic at a
concentration of 40 mg., per cent and bactericidal at 160 mg. per cent. With
a standard level of 10 units of penicillin per milliliter in brain-heart infusion broth,
a synergistic effect was observed when varying concentrations of sodium para-
aminohippurate were added. The bacteriostatic and minimal lethal zones of
sodium para-aminohippurate were reduced to 16 mg. per cent and 63 mg. per
cent, respectively, in the presence of 10 units of penicillin per milliliter of test
broth.

The converse of what has been discussed is also summarized in Table III.
To brain-heart infusion broth containing 20 to 50 mg. per cent of sodium para-
aminohippurate were added vaiying concentrations of penicillin. These were
inoculated with Veillonella gazogenes and incubated for twenty-four hours. At a
concentration of 50 mg. per cent of sodium para-aminohippurate the bacterio-
static level of penicillin remained at 10 units per milliliter in all instances, but the
bactericidal zone was progressively reduced until it reached 15 units of penicillin
per milliliter, almost appro.vimating the bacteriostatic level.

These experiments indicate a pronounced synergistic effect between penicillin
and sodium para-aminohippurate. Thus, consistent minimal lethal levels against
the infecting organism in this case could obviously be reached more readily with
the conjoint use of both drugs than could have been achieved by the use of either
one, per se.

LOEWE ET AL. : SUBACUTE BACTERIAL ENDOCARDITIS

337

SUMMARY AND CONCLUSIONS

1 . A unique case of subacute bacterial endocarditis due to Veillonella
gazogenes has been presented.

2. Massive sulfonamide therapy was ineffectual in terminating the infec-
tion.

3. Twelve courses of penicillin therapy of varying length, combined at
times with adjuvants such as sulfonamides and heparin, failed to sterilize the
blood stream although progress of the infection was retarded during the year of
this treatment. Dosages of penicillin up to 10 million units per day by the con-
tinuous intravenous route were nontoxic and well tolerated. A total of 466,
670,000 units of penicillin was used during this period.

4. In vitro studies revealed bacteriostasis for the organism at 10 units per
milliliter of streptomycin and penicillin. The minimum lethal dose was 10
units per milliliter and 30 units per milliliter for streptomycin and penicillin,
respectively.

5. With a constant concentration of 10 units per milliliter of penicillin,
the bacteriostatic and minimum lethal dose of sodium para-aminohippurate was
16 mg. per cent and 63 mg. per cent, respectively. This contrasts with bacterio-
static and lethal doses of 40 mg. per cent and 163 mg. per cent, respectively, of
sodium para-aminohippurate, per se.

6. With concentrations of sodium para-aminohippurate varying from 20
to 50 nig, per cent, the minimum lethal dose of penicillin against the infecting
organism was lowered as much as 15 units per milliliter.

7. These data were clinically applied with satisfactory results by the
simultaneous daily intravenous administration of penicillin and sodium para-
aminohippurate in doses of 10 million units and 240 Gm., respectively, over a
period of sixteen days. Heparin was also incorporated for its beneficial effect
in maintaining an uninterrupted venoclysis.

8. This is the first case in which sodium para-aminohippurate has been
used with penicillin in the actual clinical arrest of an infection otherwise highly
resistant to the action of penicillin alone.

9. The case demonstrates the need for close collaboration between the
laboratory and the clinician for optimum results.

■ The authors desire to e.vpress their appreciation of the contributions made by Miss M.
Kozak, Mr. M. Russell, and Miss F. Kashdan.

REFERENCES

1. Loewe, L., Rosenblatt, P., Greene, H. J., and Russell, M.: Combined Penicillin and Heparin
Therapy of Subacute Bacterial Endocarditis, Report of Seven Consecutive Successfully
Treated Patients, J. A. M. A. 124; 144-149, 1944.

2. Loewe, L.: The Combined Use of Penicillin and Heparin in the Treatment of Subacute
Bacterial Endocarditis, Canad. M. A. J. 52; 1-14, 1945.

3. Loewe, L.; The Combined Use of Anti-Infectives and Anti-Coagulants in the Treatment of
Subacute Bacterial Endocarditis, Bull. New York Acad. Med. 21: 59-86, 1945.

338

AMERICAN HEART JOURNAL

4. Conference on Therapy, Cornell University Medical CoHckc and the New York Hospital,
Departments of Pharmacology and Medicine, The Treatment of Subacute Bacterial Endo-
carditis, Jan. 11, 1945, New York State J. Med, 45: 1452-1459, 1945.

5. Loewe, L., Rosenblatt, P., Russell, M., and Alture-Wcrber, E.: The Superiority of the
Continuous Intravenous Drip for the Maintenance of EfTectual Serum Levels of Penicillin:
Comparative Studies With Particular Reference to Fractional and Continuous Intramuscular
Administration, J. Lab. & Clin. Med. 50: 730-735, 1945.

6. Bergey, D. H., Breed, R. _S., Murray, E. G. D., and Parker Hitchens, A.: Bergey’s Manual
of Determinative Bacteriology, Baltimore, 1939, Williams and Wilkins Co., pp. 287-288.

7. Rosenblatt, P., Alture-Werber, E., Kashdan, F,, and Loewe, L.: Method for the Ad-

ministration of Penicillin in Body Fluids, J. Bact. 40: 599, 1944.

8. Beyer, K. IL, Flippin, H„ Verwey, W. F., and Woodward, R.: The Effect of Para-Amino-
liippuric Acid on the Plasma Concentration of Penicillin in Man, J. A. M. A. 126: 1007-
1009, 1944, '

9. Loewe, L., Rosenblatt, P., Alture-Werber, E., and Kozak, M.; The Prolonging Action of
Penicillin by Para-Aminohippuric Acid, Proc. Soc. Exper. Biol. & Med. 50: 298-300, 1945.

CARDIAC OUTPUT IN HEART FAILURE

J. R. E. Suarez, M.D., J. C. Fasciolo, M.D., and A. C. Taquini, M.D.

Buenos Aires, Argentina

OINCE the pioneer work of von Plesch in 1909, * extensive research has been ,
^ done on the behavior of cardiac output in valvular, hypertensive, and coro-
nary heart diseases. Von Plesch, like most of his followers, 2 -^“ found great
variability in the cardiac output of cardiac patients with or without failure. .
Their results are likely to be criticized because of the methods used or because
basal conditions were not accurately observed. In general, however, their
results showed normal or diminished cardiac output.

Starr and his associates, using the ethyl iodide method modified by Starr
and Gamble,'’® observed that generally the cardiac output was normal in com- .
pensated cardiac patients. In patients with failure they usually found a dimin-
ished cardiac output, though in sorre the values were within normal range. They
failed to find a correlation between cardiac output and functional capacity of the
heart. Altschule and Blumgart,^® using the same method as Starr and his asso-' •
dates, observed that the cardiac output was at the lower limit of normal in a
patient with mitral, tricuspid, and aortic stenosis and insufficiency.

Grollman and his co-workers®’ investigated the possible application of the ,
acetylene technique in cardiac patients, showing that it was desirable to take at
least three samples during the rebreathing period. In their small series of patients
with severe heart failure, the cardiac output was diminished in some and within ,
the normal range in others. Using the same method, McMichael®- showed that
the cardiac output was normal in compensated cardiac patients and diminished
in those with failure, but no consistent correlation could be demonstrated be-
tween the degree of the insufficiency and the cardiac output. Taquini and his
co-workers,®® using the acetylene technique with three or four samples, studied
a series of patients with mitral stenosis, either compensated or with a mild degree ^
of failure. In their cases the figures for the average cardiac index were lower than
those for the normal controls, both in patients with normal sinus rhythm and
in those with auricular fibrillation.

. Some investigators were especially interested in finding a correlation between,
the, severity of heart failure and cardiac output, Harrison and his associates®^
and Harrison,®® using the acet 3 dene method (three or four samples), found that,
in, general the cardiac output was diminished in patients with cardiac failure.
They concluded, however, that there was no relation between the degree of the

Center of Cardiologic Kcsearch. Aarginio F. Grego Foundation. Faculty of Atwlicino. Xaiiversitv

of Bueno.s Aires, Buenos Aires, Argentina. ' - ' .

Beceifed for publication Dec. 22, ItM.*;.

3.39

340

AMERICAN HEART JOURNAL

insufficiency and the cardiac output or the arteriovenous oxygen difference.
In support of this conclusion they pointed out that, in the same patient, a clinical
improvement can be associated with increased, diminished, or no change in
cardiac output and arteriovenous oxygen difference.

McGuire, Hauenstein, and Shore,®® using the acetylene and the direct Pick
method on a small number of patients, could not find a consistent correlation
between the degree of heart failure and the diminution of cardiac output.
Later,”'®® using the three-sample acetylene method on a greater number of cases
of congestive heart failure, they observed that, as the insufficiency was m.ore
severe, the cardiac index was reduced further, with only a few exceptions which
could be readily explained on the basis of such extracardiac factors as metabolism,
venous pressure, hyperpnea, and so forth. They divided the patients into four
groups according to the severity of the congestive heart failure, noting that the
difference in cardiac index of any two consecutive groups was not statistically
significant although it was significant between the first and the last group.

Stewart and co-workers®®- ®i pointed out that a close correlation could be
drawn between the clinical condition and the cardiac output in rheumatic, hyper-
tensive, arteriosclerotic, and syphilitic heart disease. Using the three-sample
acetylene method, they showed that the average cardiac index was slightly
reduced in patients who never had experienced cardiac insufficiency, and that
' it was much lower in cases with congestive heart failure. In a group of patients
studied after recovery from failure, the figures for the average cardiac index
showed a value between those of the patients Avith compensated heart disease
and those of the patients Avith congestive failure. The clinical improvement
Avas accompanied by an increase of the cardiac output although the values of the
first group Avere not reached. These results led SteAvart and his co-Avorkers to
the conclusion that there is an inverse correlation betAA’^een the degree of heart
failure and the cardiac index.

SteAA'^art and his co-Avorkers®® found that "single lesions are not incompatible
with a fairly normal circulation at rest, but in all instances in Avhich there is
more than one lesion functional alterations appear." They held also that aortic
stenosis combined Avith other valvular lesions resulted in marked decrease in
Junction. On the other hand, aortic regurgitation seemed to be of functional
benefit A\ffien superimposed on mitral stenosis and insufficiency and resulted in
less impairment of the circulation than AA'^as found in mitral stenosis and insuf-
ficiency alone. The same authors said, "The order of magnitude of the func-
tional defect increased progressively in going from the mitral stenosis and in-
sufficiency, aortic insufficiency group, to the mitral stenosis and insufficiency
group, to the mitral stenosis and insufficiency, aortic stenosis and insufficiency
group."

SUAREZ ET AL. : CARDIAC OUTPUT IN HEART FAILURE

MATERIAL AND METHODS

A total of seventy-five determinations were made in forty-two patients.
They were grouped under the following diagnoses:

DIAGNOSIS

Mitral stenosis and insufficiency, sinus rhythm

Mitral stenosis and insufficiency, auricular fibrillation

Mitral stenosis and insufficiency, aortic insufficiency

Mitral stenosis and insufficiency, tricuspid stenosis and insufficiency.

Mitral stenosis, interauricular septal defect .

Aortic insufficiency

Aortic stenosis and insufficiency

Hypertensive and coronary' heart disease

Total

NU.MBER OF
PATIENTS

13

9

1

2

3

2

2

10

42

NUMBER CF
DETERMINA-
TIONS
23
20
1
2
5
3
5

16

75

The patients were classified according to their functional capacity at the
moment of the determinations, whether they were being treated or not, following
the criteria and nomenclature of the New York Heart Association.®* Our results
in a group of seventeen normal subjects were used as controls.

The oxygen consumption was determined by an open circuit method using
a Tissot spirometer; the air was collected in ten-minute periods. The arterio-
venous oxygen difference was determined with the acet 3 dene method of Groll-
man®2; four samples were taken during the rebreathing period. The gas analyses
were carried out in the Haldane apparatus wuth a device for the absorption of
the acetylene, and a 12 c.c. burette w'as used. All the determinations were car-
ried out under basal conditions wuth the patient sitting in a comfortable arm-
chair at an angle of 105 degrees and wuth the knees flexed. In every case the
patient had been trained to carry out the procedure beforehand.

A statistical evaluation of the results w^as carried out using the

followung equations: standard deviation —

cr =

Sd2

(n-1)

and standard

error = €

S d

n(n-l)

2

— , In groups of less than ten cases the followung

Sd2

equations w’^ere applied; standard deviation ^ / (n-3)

; and standard

error

S d^
n(n-3)

Comparing the different groups, the standard devi-

ation of the difference betw^een the averages w^as calculated according to the

equation

' F2 -1-E2
^'i II

The differences were considered statistically signifi-

cant wben they w'ere equal to or greater than three times their standard devia-
tion and very probably real wben they fell betw^een tw'O and three times their
standard deviation.

'342

AMERICAN HEART JOURNAL

RESULTS

In Tables I to V are summarized the results of all the determinations. The
average values in each group with the various lesions follow;

■ Mitral Stenosis and Insufficiency, Smus Rliytkni.

Cardiac Index; Class I, 2.27 liters per square meter per minute (four patients). Class

II, 1.99 (six patients). Class III, 1.79 (four patients).

Arteriovenous Oxygen Difference; Class I, 65.5 c.c. per liter of blood. Class II, 66. -3.
Class III, 80.1.

Heart Rate; Class I, 68 per minute. Class II, 69. Class III, 88.

Systolic Output per Square Meter; Class I, 34.1 c.c. per square meter of body surface.
Class II, 29.0. Class III, 20.4.

Mitral Stenosis and Insufficiency, Auricular Fibrillation.

Cardiac Index; Class II, 1,99 liters per square meter per minute (nine patients). Class
. Ill, 1.28 (1 patient).

Arteriovenous Oxygen Difference; Class II, 70.7 c.c. per liter of blood. Class III,

110 . 6 .

Heart Rate; Class II, 72 per minute. Class III, 78.

Systolic Output per Square Meter; Class II, 28.3 c.c. per square meter of body surface.
Class III, 16.5.

Mitral Stenosis and Insufficiency, Aortic Insufficiency.

Cardiac Index; Class II, 2.02 liters per square meter per minute (one patient).
Arteriovenous Oxygen Difference; Class 11, 65.6 c.c. per liter of blood.

Heart Rate; Class II, 73 per minute.

Systolic Output per Square Meter: Class II, 27.5 c.c. per square meter of body surface.

Mitral Stenosis and Insufficiency, Tricuspid Stenosis and Insufficiency.

Cardiac Index; Class II, 1.95 liters per square meter per minute (one patient). Class
'IV, 1.56 (one patient).

Arteriovenous Oxygen Difference: Class II, 74,0 c.c. per liter of blood. Class IV, 97.4.
Heart Rate: Class II, 82 per minute. Class IV, 98.

Systolic Output per Square Meter: Class II, 23.7 c.c. per square meter of body surface.
Class IV, 15.9.

Mitral Stenosis and Insufficiency, Interauricular Septal Defect.

Cardiac Index: Class II, 2.31 liters per square meter per minute (two patients). Class
HI, 1.57 (one patient).

Arteriovenous Oxj^gen Difference: Class II, 59.7 c.c. per liter of blood. Class HI, 88.0,
Heart Rate: Class II, 59 per minute. Class HI, 70.

Sj'stolic Output per Square Meter: Class II, 39.1 c.c. per square meter of body surface.
Class III, 22.2.,

Aortic Insufficiency.

Cardiac Index; Class I, 2.94 liters per square meter per minute (one patient). Class

III, 2.27 (one patient).

Arteriovenous Oxj'gen Difference: Class I, 53.3 c.c. per liter of blood. Class III, 68.1.

- Heart Rate: Class I, 76 per minute. Class III, 70.

Systolic Output per Square Meter: Class I, 38.8 c.c. per square meter of body surface.
Class III, 32.3.

Aortic Stenosis and Insufficiency. ^

Cardiac Index: Class II, 2.02 liters per square meter per minute (one patient). Class
III, 1.68 (one patient).

Arteriovenous Oxygen Difference; Class II, 61.6 c.c. per liter of blood. Class III, 86.8.
Heart Rate: Class II, 74 per minute. Class III, 67.

Systolic Output per Square Meter: Class II, 27,2 c.c. per square meter of body surface.

SUAREZ ET AL. : CARDIAC OUTPUT I N HEART FAILURE 343

Hypertensive and Coronary Heart Disease.

Cardiac Index: Class I, 2.66 liters per square meter per minute (one patient). Class
11, 2.11 (three patients). Class III, 1.82 (five patients). Class IV, 1.60 (two patients):

Arteriovenous 0.xygen Difference: Class I, 49.4 c.c. per liter of blood. Class II, 61.5.
Class III, 7.5.3. Class IV, 88.9.

Heart Rate: Class I, 73 per minute. Class II, 63. Class III, 72. Class IV, 77.

Systolic Output per Square Meter: Class I, 36.4 c.c. per square meter of bodv surface.
Class 11, 33.7. Class III, 26.0. Class IV, 21.0.

In the calculation of these results, the various determinations on the same
individual were averaged, provided that the functional capacity had not changed.
In the few cases in which a change was observ'ed in the functional capacity, the
results obtained in each case were considered separately within the corresponding
capacity group.

With few exceptions, which will be discussed later, the data show that the
average values of the patients with different lesions are similar provided the
functional capacity is the same. Fig. 1, where the average cardiac index of the.

■ Mitr sten. and insuff ,intef'auric sept. def.
♦ Aortic insufficiency
^ •’ sten. and insuff.

A. Hy pert, and coronary heart disease

ptjr 1 Cardiac indc.v of normal patients and those with heart disease. Each sj-mbol represents

the average cardiac index of each case. The horizontal lint^ represent, the average cardiac index of all
the cases 'of each group (aortic insufficiency was not included).

• Mitr sten; and insuff,,3inus rhythm
Q « " ' ” , auric, fibrillat.

Q " " " , " , aortic insuff.

Q[ Mitr and tricusp. sten. and insuff.

Table L Mitral Stenosis and Insufficiency, Sinus Rjivtiim

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Table VI. Average Results Obtained Grouping the Cases According to Their Functional Capacity

SUAREZ ET AL. ; CARDIAC OUTPUT IN HEART FAILURE

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349

350

AMERICAN HEART JOURNAL

normal and of the four cardiac groups is represented by a horizontal line, shows
that the individual values are evenly distributed regardless of the diagnosis.
In Table VI the results obtained by grouping the cases according to their func-
tional capacity, disregarding their diagnosis, are presented.

DISCUSSION

The determination of cardiac output by a foreign gas method in patients
with interauricular septal defect and mitral disease can be criticized, since in
this condition the blood which passes from the left to the right auricle produces
an abnormally rapid recirculation. We do not know whether or not in other
similar cases this rapid recirculation can be an important source of error. In our
patients it seems to have been of little importance since we could obtain similar
values in two pairs of successi\'e samples of the same rebreathing period.

Patient R. S. (uncomplicated aortic regurgitation. Class I, No. 29) showed a
cardiac index well above the normal limit. Although the first possible e.\plana-
tion of this finding is a modification of the basal conditions, this could be ruled
out because the patient was quiet and cooperative and the basal metabolic rate
was normal. On the other hand, Starr and Gamble-*® stated that similar results
have been obtained by Ewig and Hinsberg,*® Starr and collaborators,^' Syllaba,®*
and Bock.®® Even though the methods employed by some of these authors are
open to objection, the fact that similar results were obtained b>- several investi-
gators in patients without failure, where special technical difficulties are not
expected, gives support to our findings.

Since the possibility exists that in aortic insufficiency the valvular defect
might modify the cardiac index independently of the functional capacity, we
eliminated patients with uncomplicated aortic insufficiency in calculating the
average cardiac index of each functional group.

The difference between the cardiac index of normal subjects (2.27)
and that of cardiac patients of Class I (2.35) is 0.08 ± 0.20, which is not
statistically significant. The difference between the average cardiac index
of patients of Class I (2.35) and of patients of Class II (2.03) is 0.32 ± 0.20,
which likewise is not significant. Comparison of the normal persons (cardiac
index, 2.27) with patients of Class II (cardiac index, 2.03) shows that the
difference of the averages (0.24 ± 0.078) equals slightly more than three
times its standard deviation, which is highly significant. Although the
difference between patients in Class I and those in Class II is greater
than that between normal persons and patients in Class II, it is not statistically
significant in the former case because of the small number of patients in Class I
(five patients). Comparison between tlie averages of individuals in Class II
(cardiac index, 2.03) and those in Class III (cardiac index, 1.73) shows that the
difference (0.30 ± 0.10) equals three times its standard deviation and is, there-
fore, statistically significant. Between persons in Class III (cardiac index, 1.73)
and persons in Class IV (cardiac inde.x, 1.58) the difference is 0.15. We did not
determine a statistical difference with Class IV because of the small number of
cases in the latter.

SUAREZ etal;: cardiac output in heart failure 851

The results obtained in our series of hypertensive, coronar^u and valvular
diseases, excepting uncomplicated aortic regurgitation, led to the conclusion
that the patients belonging to Class I (with no limitation of physical activity)
maintain at rest a normal cardiac output. Patients of Class II (slight limitation
of physical activity) on the whole have a diminished cardiac output even at rest,
but their cardiac index is significantly greater than that of patients in Class III
(marked limitation of physical activity). The small number of patients in Class
IV (unable to carry on any physical activity without discomfort) prevented our
drawing conclusions concerning this group, in spite of the low value of the average
cardiac index, i. e., 1.58 liters per square meter per minute (the lowest value of
any class). In patients with congestive heart failure, comparable to those in-
cluded in Class IV, McGuire and his co-workers*® found an average cardiac index
of 1.52 ± 0.06 and Stewart and his associates*^ found an index of 1.42. These
results obtained with the acetylene method, taking three samples, give support
to our findings and indicate that in patients in Class IV the cardiac output
reaches its lowest level.

The normal values which we obtained in patients in Class I are in accord
with the observations of McIVichaeF^ made in the same type of patients and,
differ from the results of Stewart and his associates,*^ who state that patients with
organic heart disease without failure have a decreased cardiac index.

The above results show that most of the patients with heart failure have
a diminished cardiac output and suggest that there is an inverse correlation
between the degree of cardiac failure and the cardiac output. However, in some
subjects, in spite of their cardiac failure, the cardiac output was within normal
values, but this occurred less frequently in the more advanced stages of the disease.
The possibility exists that, in some cases, even though there is a diminution of the
cardiac output, the values reached are within the lower normal limits, for instance,
an index of 2.5 to 2.0, the latter still being a normal figure. It is also possible that
an increase in the metabolic rate, such as is frequently seen in heart failure, or
variations in the other mechanisms which control the cardiac output (venous
pressure, pulmonary ventilation, and so forth) may explain the differences
found in the patients included in each class. The general trend of the cardiac out-
put towards lower values in heart failure and the importance of the extracardiac
factors are at present accepted by all investigators of this subject (Altschule,**
McGuire and collaborators,*"'** IMcMichael,** Harrison,** Stewart and his asso-
ciates,**’ ** and others).

Some observers, however, notably Harrison and his co-workers*’ and Harri-
son,** believe that there is no correlation between the cardiac output and the
degree of heart failure, and attribute this lack of correlation to the influence of
the various extracardiac factors. On the other hand, several investigators
(Stewart and collaborators**’ and McGuire and collaborators*®- **) admit that '
a correlation can be drawn between cardiac output and the functional capacity of
the heart, the exceptions being explained on the basis of extracardiac factors.
Our findings support these conclusions. It should be emphasized that the corre-
lation noted by Stewart and collaborators*” between the number or type . of
valvular lesions and the functional alterations was not seen in our study.

352

AMERICAN HEART JOURNAL

The arteriovenous oxygen dilTerence of patients in Class I (62.2 c.c. per liter)
is approximately the same as that of normal subjects (60.4 c.c. per liter). The
average values of the arteriovenous oxygen ditTerencc of patients of Class I and
Class II (66.9 c.c. per liter) do not differ significant Ij' (4.7 ± 6,79). On the other
hand, the difference between the average values for patients of Class 11 and that
of the normal persons is 6.5 ± 2,57, which means that the difference is \’ery' prob-
ably real. The arteriovenous oxygen difTcrence of patients in Class III (81.0)
compared with patients in Class II shows a dilTerence of 14.1 i 3.37, which is
statistically significant. Patients in Class IV have an arteriovenous oxygen
dilTerence of 91.8, i. e., 10.8 greater than that of jiaticnts in Class III. No
statistical determinations were carried out in Group I\' because of the small
number of cases.

These figures show that cardiac patients without failure maintain a practi-
cally normal arteriovenous oxygen difference. Where v'arious degrees of failure
exist, the arteriovenous oxygen dilTerence increases, suggesting a correlation
with the degree of the failure. The arteriovenous oxygen dilTerence is an im-
portant index of the circulatory function. However, the wide .scattering of the
different values within normal as well as within cardiac groups makes neces.sary
a great deal of caution in judging individual results.

The heart rate of patients with mitral stenosis shows a different behavior
when compared with the behavior of the rale of patients with other types of
heart disease. In calculating the averages in the group of patients with a mitral
lesion, we excluded Case C. T. (mitral insufficiency and stenosis, sinus rhythm,
No, 1, Class I) because of the slightly elevated metabolic rate which, in the
absence of heart failure, indicated the possibility of a mild degree of hyper-
thyroidism. We considered +15 per cent to be the upper normal metabolic
rate. For similar reasons we used only the fourth and fifth determinations made
in Patient R. C. (mitral stenosis and insufficiency, auricular fibrillation, No. 15,
Class II), whose basal metabolic rate was normal.

The results obtained show that in the cases with failure there was a general
trend toward an increased heart rale, although there were differences within
the various diagnostic groups. Patients Avith mitral \'alve lesions with no failure
(Class I) showed a normal heart rate; those with various degrees of failure
(Classes II, III, and IV) pre.senled an increased cardiac rate Avhich was propor-
tional to the degree of the failure. On the other hand, in the other types of heart
disease we could not obserA^e any relation betAveen functional capacity and heart
rate.

The systolic output per square meter of body surface, up to noAv used
almost exclush'^ely by ScandinaAu'an inA'esligators, proA'ed to be a useful index of
circulatory modifications in heart failure. As the results did not show important
differences in the A^arious types of heart disease, it seemed reasonable to consider
together all the cases of \mlvular, liyperlensiA-e, and coronary heart disease. The
patients belonging to Class I had an aA'erage stroke A’olume per square meter of
35.3 C.C., nearly equal to that of normal subjects (35.4). Patients in Class II
had a lower a\’’erage (29.8), but the difference betAveen patients in Class II and

SUAREZ ETAL.: CARDIAC OUTPUT IN HEART FAILURE 353

, / ■

those in Class I (5.5 ± 3,04) was not statistically significant. This may have
been due to the small number of cases in Class I. The difference in stroke volume
in normal persons and in patients in Class II was 5.6 ± 1.44 (statistically
significant); the same holds for the difference between patients in Classes II and
III (6.0 ± 1.73). Subjects in Class IV showed the lowest index (19.3), with a
difference with respect to patients in Class III of 4.5. The figures suggest that
an inverse correlation does exist between systolic output and the degree of heart
failure.

SUMMARY AND CONCLUSIONS

The cardiac output under basal conditions was studied in forty-two patients
with different types of valvular, hypertensive, or coronary heart disease, and in
seventeen normal subjects. Grollman’s acetylene m.ethod with four samples was
used. The cardiac patients were grouped in four classes according to their
functional capacity, following the criteria and nom.enclature of the New York
Heart Association. The following results, expressed as an average for each group,
were obtained :

1. The cardiac index was 2.27 liters per square meter per minute ± 0.06

in the normal control group, 2.35 + 0.19 in patients in Class I, 2.03 ± 0.05 in

patients in Class II, 1,73 ± 0.087 in patients in Class III, and 1.58 in those
in Class IV.

The differences found were statistically significant between the normal group
and those in Class II, and between persons in Classes II and III, suggesting an
inverse correlation between the degree of cardiac failure and the cardiac output.

2. The arteriovenous oxygen difference was 60.4 c.c. per liter of blood

+ 1.78 in the normal group, 62.2 + 6.53 in patients in Class I, 66.9 ± 1.85 in

those in Class II, 81.0 + 3.96 in persons in Class III, and 91.8 in patients in Class
IV.

The difference between normal subjects and subjects in Class II was probably
real, and the difference was statistically significant between subjects in Class II
and subjects in Class III. This suggested a direct correlation between the degree
of cardiac failure and the increase in arteriovenous oxygen difference.

3. The behavior of the heart rate was different in patients with mitral
valve disease and in those with aortic, hypertensive, and coronary artery disease.
The heart rate in the normal group averaged 63 per minute.

In the mitral patients the heart rate was 63 per minute in those in Class I,
70 in those in Class II, 83 in those in Class III, and 98 in Class IV. The heart
rate in patients with other types of disease was 74 in those in Class I, 66 in those
in Class II, 7l in those in Class III, and in 77 in patients in Class IV.

Although statistical determinations of these data were not carried out, the
corresponding results in each group seemed to indicate-that, in the mitral patients
without failure (Class I), the heart rate was within the normal range, increasing
in the presence of failure and according to the severity of the latter. In the
aortic, hypertensive, or coronary groups, the behavior of the cardiac rate was
rather irregular.

354

AMERICAN HEART JOURNAL

4. The systolic output per square meter of body surface was 35.4 c.c. ± 0.76
in the normal group, 35.3 + 2.81 in patients in Class I, 29.8 + 1.14 in those in
Class II, 23.8 + 1.29 in those in Class III, and 19.3 in patients in Class IV.

The differences were statistically significant between the normal group and
those in Class II and between patients in Classes II and III, suggesting that an
inverse correlation exists between heart failure and systolic output.

We wish to express our gratitude to Dr. C. S. BurwcII and his co-workcrs for teaching the
technical details of the four-sample acetylene method to one of us (A. C. T.).

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et de chir. 4: 853, 1933.

355

SUAREZ ET AL. ; CARDIAC OUTPUT IN HEART FAILURE

20. Cordier, V., Enselme, J., and Nury, D.: Etude des echanges respiratories et du debit
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22. Henderson, Y., and Haggard, H. W.t The Circulation and its Measurement, Am. J. Phy-
siol. 73: 193, 1925.

23. Kininmonth, J. G.: The Circulation Rate in Some Pathological States, With Observations
on the Effect of Digitalis, Quart. J. Med. 21: 277, 1928.

• 24. Lauter, S., and Baumann, H.: Zur Theorie der Herzinsuffizienz und der Digitaliswirkung,
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25. Ringer, M., and Altschule, M. D.; Studies on the Circulation. 11. Cardiac Output in
Diseases of the Heart and Under the Influence of Digitalis Therapy, Am. Heart J. 5: 305,
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26. Kroetz, C. : Messung des Kreislaufminutenvolumens mit Acetylen als Fremdgas. Ihre
bisherigen Ergebnisse bei arteriellem Hochdruck und bei Dekompensation des Kreislaufs,
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27. Grassmann, W., and Herzog, F.: Die Wirkung von Digitalis (Strophanthin) auf das Minu-
ten-und Schlagvolumen des Herzkranken, Arch. f. exper. Path. u. Pharmakol. 163: 97, 1931.

28. Stewart, H. J.; Effect of Giving Digitalis on the Volume Output of the Heart and its Size
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31. Lysholm, E., Nylin, G., and Quarna, K.: The Relation Between the Heart Volume and
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32. Oettinger, I., and Masel, I.; Schlag-und Minutenvolumen bei Mitralfehlern, Deutsches
Arch. f. klin. Med. 177: 661, 1935.

33. Goldbloom, A. A.: Clinical Studies in Circulator}' Adjustments. III. Clinical Evalua-
tion of Cardiac Output Studies, Internal. Clin. 3; 206, 1936.

34. Goldbloom, A. A., and Lieberson, A.: Clinical Studies in Circulatory Adjustments. V.
Clinical Evaluat'on of Cardiodynamic Studies, Am. J. M. Sc. 197: 182, 1939.

35. Nielsen, H. E.; Clinical Investigations Into the Cardiac Output of Patients With Con-
pensated Heart Disease During Rest and During Muscular Work. Acta med. Scandinav.
91: 223, 1937.

36. Lequime, J.: Le debit cardiaque, etudes experimentales et cliniques, Acta med. Scandinav.,
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37. Espersen, T.; Studies on the Cardiac Output and Related Circulatory Functions, Especi-
ally in Patients With Congestive Heart Failure, Acta med. Scandinav. 108: 153, 1941.

38. Hamilton, W. F., Moore, J. W., Kinsman, J. M., and Spurling, R. G.: Studies on the
Circulation; Further Analysis of the Injection Method, and of Changes in Hemodynamics
Under Physiological and Pathological Conditions, Am. J, Physiol. 99; 534, 1932.

39. Kmsman, J. M., Moore, J. W., and Hamilton, W. F.: Studies on the Circulation : Analysis
of Some Problems of the Circulation in Man in the Normal and in the Pathological States
by the Use of the Injection Method, Kentuck}' M. J. 31: 285, 1933.

40. Kinsman, J. M., and Moore, J. W.: The Hemodynamics of the Circulation in Hyperten-
sion, Ann. Int. Med. 9: 649, 1935.

4rl. Starr, I.: Clinical Studies With the Ballistocardiograph ; in Congestive Failure, on Digi-
talis Action, on Changes in Ballistic Form, and in Certain Acute Experiments, Am. J. M.
Sc. 202: 469, 1941.

42. Starr, L, and Schroeder, H. A. ; Ballistocardiogram. II. Normal Standards, Abnormali-
ties Commonly Found in Diseases of the Heart and Circulation, and Their Significance,
J. Clin. Investigation 19: 437, 1940.

43. Seymour, W. B., Pritchard, W. H., Longley, L. P., and Hayman, J. M., Jr.: Cardiac Out-
put, Blood and Interstitial Fluid Volumes, Total Circulating Serum Protein, and Kidriey
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1942.

44. Lauter, S.; Kreislaufprobleme, Miinchen. med. Wchnschr. 77; 526, 1930.

45. Padilla, T., Cossio, P., and Berconsky, I.: Sondeo del corazon. III. Determinacidn del
volumen minute circulatorio, Semana med. 2; 445, 1932.

356 AMERICAN HEART JOURNAL

46 Starr, I., Jr., Collins, L. H., Jr., and Wood, F. C.: Studies of the Basal Work and Output
of the Heart in Clinical Conditions, J. Clin. Investigation 12: 1.1, 19.1.1.

47 Starr, I.,'jr., Donal, J. S., Margolies, A., Shaw, R., Collins, L. H., Jr., and Gamble, C. J.:
Studies of the Heart and Circulation in Disease; Estimations of Basal Cardiac Output,
Metabolism, Heart Size and Blood Pressure in 2.15 Subjects, J. Clin. Investigation 1.1: 561,

1934.

48 Starr, I., Jr., and Gamble, C. J.; Cardiac Output in Common Clinical Conditions: and the
Diagnosis of Myocardial InsufTiciencv by Cardiac Output Methods, Ann. Int. Med. 9; 569,

1935.

49. Starr, I., Jr., and Gamble, C. J., An Improved Method forjhe^Detcrminalion of Cardiac
Output in Man by Means of Ethyl Iodide, Am. J. Physiol. <17; 450, 1928.

50. Atschule, M. D., and Blumgart, H. L.: The Circulatory Dynamics in Tricuspid Stenosis;
Their Significance in Pathogenesis of Edema and Orthopnea, Am. Heart J. Kl: 589, 1937.

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Failure. XXIV. A Critical Study of Methods for Determining the Cardiac Output in
Patients With Cardiac Disease, J. Clin. Investigation 12: 751, 1933.

52. McMichael, J.: Output of Heart in Congestive Failure, Quart. J. Med. 7: 3.11, 19.18.

53. Taquini, A. C., Sufirez, J. R. E., and Fasciolo, J. C.: Capacidad funcional en la cstenosis
mitral. Rev, Argent, de cardiol. 9: 279, 1943.

.54. Harrison, T. R., Friedman, B., Clark, G., and Resnik, H.; The Cardiac Output in Rela-
tion to Cardiac Failure, Arch. Int. Med. .51: 239, 1934.

55. Harrison, T. R.: Failure of the Circulation, Baltimore, 1939, Williams and Wilkins Com-
. pany.

56. McGuire, J., Hauenstein, V., and Shore, R.: Cardiac Output in He.art Disease Determined
by the Direct Fick Method, Including Comparative Determinations by the Acetylene
Method, Arch. Int. Med. 60: 1034, 1937.

^7. McGuire, J., Shore, R., Hauenstein, V., and Goldman, F.: Influence of Exercise on Cardiac
Output in Congestive Heart Failure, Arch. Int. Med. 63; 469, 1939.

58. McGuire, J., Shore, R., Hauenstein, V., and Goldman, F.: Relation of Cardiac Output
to Congestive Heart Failure, Arcli. Int. Med. 63; 290, 1939.

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pensation and Decompensation in the Same Individual, Am, Heart J. 16; 449, 19.18.

60 . Stewart, H. J., Deitrick, J. E., Watson, R. R., Wheeler, C. H., and Crane, N. F.: The
Efifect of Valvular Heart Disease on the Dynamics of the Circulation. Observation Before,
During and After the Occurrence of Heart Failure, Am. Heart J. 16: 477, 1938

61. Stewart, H. J., Crane, N. F., Watson, R. F., Wheeler, C. H., and Deitrick, J. E.: The
Cardiac Output in Congestive Heart Failure and in Organic Heart Disease, .Ann. Int. Med.
13: 2323, 1940.

62. Grollman, A.; The Determination of the Cardiac Outinit of Man by the Use of Acetylene,
Am. J. Physiol. 88; 432, 1929.

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nosis of Diseases of the Heart, N. Y. Tuberc. & Health Assoc., 1939.

64. Syllaba, J.: Bull. int. Acad. Sci. Bohemo. Prague, 1934. Quoted by Starr, I., Jr., and
Gamble, C. J.: Ann. Int. Med. 9: 569, 1935.

65. Bock, H. E.: Das Minutenvolumen des Herzens im Liegen und .Stehen, Ztschr. f. d. ges.
exper. Med. 92: 782, 1934.

66. Altschule, M. D.; The Pathological Physiology of Chronic Cardiac Decompensation,
Medicine 17: 75, 1938.

f

RENIN IN ESSENTIAL HYPERTENSION

Alberto C, Taquini, M.D., and Juan Carlos Fasciolo, M.D.
Buenos Aires, Argentina

^ I ^HERE has been much discussion recently on the part which the kidney plays

in the production of human hypertension. Recent work seems to indicate
that renin is the pressor substance involved in the mechanism of renal hyper-
tension. Renin has been found in the arterial and renal venous blood of dogs
having hypertension of recent onset with severe reduction of the renal blood flow
but not in the renal or arterial blood of chronically hypertensive dogs.^ Using
the method of Leloir and his co-workers- we were able, in 1943,^ to detect renin
in two patients who had severe acute glomerulonephritis. These findings agree
with those of Dexter and Haynes'* who, with a similar method, detected renin
in one patient with eclampsia, two with severe pre-eclampsia, and one with
fulminating glomerulonephritis, but not in patients with other types of hyper-
tension.

It seemed appropriate to repeat these investigations, using for the detection
of renin the indirect method of Munoz and his associates.® This method is capable
of detecting about 0.1 unit of human renin in 10 c.c. of plasma. Its sensitivity
is about five to ten times greater than the direct method of Leloir and his co-
workers. ^

MATERIAL AND METHODS

This investigation was carried out on twenty-three hypertensive patients.
In all of them the diagnosis was essential hypertension. The existence of medical
or surgical renal disease or of other known causes of hypertension were excluded
as far as possible. The patients were observed over long periods of time, and
several determinations of the blood pressure were made. The figure that appears
in the table represents the average. All of the patients belonged to Groups II,
III, and IV of the Keith, Wagener, and Barker classification.® Seven patients
'were in Group II, eight were in Group III, and eight were in Group IV. Five
patients in the last group were in an advanced stage of malignant hypertension
and died soon after the estimation of renin was made.

Blood was taken in most cases by venous puncture and in some by arterial
puncture. Sodium citrate or heparin was used to prevent coagulation. The
blood was immediately centrifuged. The plasma was transferred to a tube and
the determinations were carried out within a few hours. Sometimes the esti-
mations were deferred for a day or two ; the plasma was kept in the icebox in the
meantime.

Center of Cardiologic Research, Virglnio F. Grego Foundation. Faculty of Medicine, University
of Buenos jVires, Buenos Aires, Argentina.

Received for publication Dec. 22, 1945.

357

358

AMERICAN HEART JOURNAL

For the detection of renin, the method of Munoz and collaborators® was
used. The amount of renin is estimated by measuring the amount of hyper-
tensinogen which it destroys during a four-hour incubation period. A measured
amount of boyine hypertensinogen (about 1 unit) is incubated with 10 c.c. of
the human plasma in which the determination is to be carried out; red cell
hypertensinase and 0.6 c.c. of a 1 per cent solution of merthiolate (Lilly) as a
preservative are added. A control tube is prepared in which human plasma and
bovine hypertensinogen are incubated separately (Fig. 1).

CZ] BOVINE HYPERTENSINOGEN • HUMAN RENIN
HUMAN HYPERTENSINOGEN O SWINE RENIN
IB HYPERTENSIN B HYPERTENSINASE

Fig. 1. — Diagram sho^ring the reactions involved in the assay of human renin. The tube in which
the determination is to bo carried out is incubated four liours at 37°C. During tins period, human
renin, if present, transforms part of the hypertensinogen (bovine and human) into hypertensin, which
will be destroyed by the hypertensinase present. These reactions have been represented in two steps,
separated by the dotted line. Actually, they occur simultaneously. .A.fter the four-hour period, the
bovine hypertensinogen left is estimated by Incubating the plasma for seven minutes with swine renin
which does not act upon human hypertensinogen. The hypertensin formed is estimated by its pressor
effect when injected into an anesthetized dog intravenously. In the control tube, human plasma and
bovine hypertensinogen are incubated separately. This is represented in the, diagram by the hori-
zontal line dividing the control.

During the four-hour incubation period, renin,, if present, transforms part
of the bovine and human hypertensinogen, and the hypertensin that is formed
is destroyed by the hypertensinase. The bovine hypertensinogen remaining is
then estimated; advantage is taken of the specificity of pig renin. An excess
of pig renin transforms all of the bovine but none of the human hypertensinogen
into hypertensin in seven minutes. Because of the short incubation time, the
hypertensin formed is not destroyed by the hypertensinase. After precipitation
with alcohol, the hypertensin content of each tube is estimated by the extent to
which it raises blood pressure in the anesthetized dog. Fig. 1 presents a graphic
description of the reactions involved.

TAQUINI AND FASCIOLO: RENIN IN ESSENTIAL HYPERTENSION

359

By the use of the present method, amounts of renin as small as 0.1 unit*
in 10 c.c. of plasma can be detected semiquantitatively. Three tubes were pre-
pared. The first, hereafter referred to as the sample tube, contained the -patient’s
plasma, bovine hypertensinogen, and hypertensinase, as 'described before. Tube
2 contained 10 c.c. of plasma, and Tube 3 contained the bovine hypertensinogen.
The three tubes were incubated at 37°C. for a period of four to eleven hours,
after which the contents of Tubes 2 and 3 were mixed to make the control tube.
Three cubic centimeters of pig renin were added to the sample tube and to the
control tube, and both were incubated for seven minutes. In other cases a

fourth tube was added, containing human plasma (10 c.c.), bovine hypertensino-
gen, hypertensinase, and a measured amount of human renin (about 0.1 to 0.2
unit). We shall refer to this fourth tube as the standard tube. Determinations
on the contents of this tube were carried out as in Tube 1.

After the short incubation period, the contents of the tubes were precipi-
tated with 3 volumes of 95 per cent alcohol, the alcohol was distilled off in vacuo,
and the aqueous residue was injected intravenously into an anesthetized dog.
The blood pressure rises, in millimeters of mercury, were recorded on a smoked
drum.

RESULTS

Table I summarizes the results. In every case the results are given accord-
ing to the order in which the samples were injected into the dog. Since the
sensitivity of the animal changes with time, as shown by the pressor response to
a unit of hypertensin, it is important to know when the injection is made in
order to compare the rise of pressure resulting from the injection of the solution
in both the sample and control tubes.

The ratio

mm. Hg rise of sample tube

X 100 was calculated as follows: If

mm. Hg rise of control tube
the sample and the control tubes were tested, one immediately after the other,
the rises in blood pressure were compared directly, even if the sensitivity of the
dog changed, as indicated by a change in pressor response to 1 unit of hyper-
tensin injected before and after the samples. If a standard tube containing renin
was injected between the sample and the control tubes, the pressor response of
both sample and control tubes was compared with the nearest hypertensin unit

and the calculated ratio — - . .. -was compared as before. In the ratio

standard with renin
control tube

unit of hypertensin
X 100, the rises in blood pressure were directly compared.

For example, in Case A. de R., the rises in blood pressure in millimeters of
mercury were as follows: unit of hypertensin = 30; sample tube = 15; standard
with renin = 8; control = 16; hypertensin unit = 32. We first calculated the

*A unit of renin is the amount which, when incubated two hours with an o.-cccss of hynertensinoir.^n
yields 0.5 unit of hypertensin. ■'*

^ w (n

5 5^ Z
® z t” a

O 0\ «0 Ot^OiOO\

lo >0 ro O ^ to to CO

to

VO Tji

to I 5*

„ O !« £

o-&^

§ W H

r^0\0'0r^0c<5'00f0"d<00»-i>0p00t~0l000— <ooroo
^rO*00’“<O^T}<00^*^0'— ‘'^':^00 O'CN O ■*-< O O O

a o « £

^ H s

o ^ ^

^ ^ w

S W H

o o

rt< CO CO

O 00 ^
to r)> ro

00 o tso <N

rji CO ro

4, a a

5 O M
p « D
o H H

^00©t^lO'00\tOCOlOCOOOOt^'OlOt^*d^CSCVJOOOTi<00
•^^CS^CN^CS'^CSCOCN|fO^C*^CvlCOT-»r-iC^fOCO-tf'COCMrvJC>3

CNCOCO-^COCSC^JCN

uyst^ —

Ov

CN

tjy: -M-

O Cs
CN

esiOOOOiOCOCNCO'OcO'^OOOOOi^tOCNOOCNOOOOO

rMCNCOtOCO'-HCOCStMCOCOCN'-^COCOtO^'-'CS'^COCO'^CS^CS

^ J. H,

n - ^

^ z >*

OscSvOvOOOcoOOtO'Ori^OOOOcOOCNOOOOCOOOCOO

CSCNCOV^^cort<CNCO'^tOCOCOCOtO'OrOTt‘cO'Ot^^T}<coCM'^

S S y "y

§ S 2 j

S H g 9 o

V3 <1 H

a a ^ «

g§^ 5

OOtOvOOOlOO

CNCNCOescO'^'^CN

lOOOOOOOOO

OOOOnOvC^CN'O'^

^C^i-H^CNCNCNC'J

OOOOOOOOOOtoOO

iOTt<— ‘C^jr^C'-'TfNOtOCOCNVO

O to O O O O to to O O to o c o
\0 CO to O CO 00 to to

r^lCNCSCSCSCSCSCSCSCSCNCNCS CN

, ^ u-4 H-4 r; > >

. u u

'^.(U„0 Ji o ■ -^T+T

*The pressor responses are tabulated according to tho order in which the samples wore injected into the anesthetized (iog.
tMalignant hypertension.

iWith 0.002 c.c. of a human renin solution containing .lO to 00 units per cubic centimeter.

SWith O.OQo c c. of a human renin solution containing 20 to 30 units per cubic centimeter.
llWith 0.01 c.c. of a human renin solution containing 20 to 30 units per cubic centimeter.

TAQUmi AND FASCIOLO : RENIN IN ESSENTIAL HYPERTENSION 501

sample tube 15 „ „ , control tube 16

ratio — : ^ = — = O.a and = — =05 usine

unit of hypertensin 30 unit of hypertensin 32 ‘ ^

the nearest value obtained for the unit of standard hypertensin. Then the ratio

sample tube

control tube

standard with renin ... o __ , . j- u j

X 100 = — X 100 — 50, the rises were directly compared.

control tube 16

Table I shows that in 18 of the 26 cases, the ratio X 100

control tube

ranged between 100 and 115, indicating that both tubes contained approximately
the same quantities of hypertensinogen, which in turn indicates that renin was
not present in the sample plasma. In two cases the diminution of the hyper-

X 100 = X 100 = 100 was calculated.
0.5

For the ratio

Pig. 2. — Ordinates represent the values of the ^ ratios. White columns are the

rntinc! rorrcsDonciing to the sample tubes; black columns represent the ratios of the tubes to which a
small amount (0.1 to 0.2 unit) of human renin was added (standard tube). The shaded columns repre-
sent a ratio of 100. Values under 100 indicate the presence of renin. For interpretation of the data on
the two patients in whom values were low, as indicated by short wliite columns, see text. The figures
on the bottom of the columns are the values of the blood pressure of each patient.

White columns are the

362

AMERICfVN HEART JOURNAL

tensinogen in the sample tube suggested the presence of renin. In one of them,
however, a duplicate determination gave no indication of the presence of renin.

In six cases the ratio ranged between 117 and 150. This may have been
due to changes in the sensitivity of the dog to hypertensin, especially in the
extreme cases with a ratio of 146, 150, and 143. In these cases, no tests with
the standard hypertensin unit were made after the injection of the control tube.
On the whole, the results seem to indicate a small increase of pressor action in
the sample tube. At present we are unable to explain these results.

All except one of the standard tubes with added human renin showed a ratio
ranging from 82 to 35. This indicated that the minute amount of renin added
(0.1 to 0.2 unit) was, with only one exception, easily detected.

DISCUSSION

Using the methods available, renin has not been detected in the plasma of
patients in either the benign or the malignant phase of essential hypertension.
These findings, however, do not disprove the renal origin of human hypertension.
Actuallj% renin has been detected in the plasma of dogs after a short period of
complete ischemia of the kidney," and in the renal and arterial blood in the acute
phase of hypertension produced by partial but severe ischemia of the kidney.^
On the other hand, renin has not been demonstrated in the renal or arterial
blood of chronically hypertensive dogs.** ® In the human being, small amounts
of renin were found in the renal vein after a short period of complete ischemia*
and in the acute hypertension of a few cases of eclampsia and fulminating glomeru-
lonephritis'* but not in chronic hypertension. Since the results obtained in human
hypertension agree Avith those obtained in experimental renal hypertension of
the dog, Ave can conclude that the absence of renin cannot rule out the renal
origin of essential hypertension.

The fact that it has not been possible to detect renin in the blood of chroni-
cally hypertensiA'^e dogs or of patients Avith essential hypertension neither sup-
ports nor negates the hypothesis that renin is the pressor substance inA'oh^ed.
W'Tiether renin is present in such minute amounts tliat it cannot be detected by
the method used, or Avhether it does not exist at all in tliese patients, cannot be
decided at present.

Since renin is found by existing methods in the acute phase of renal hyper-
tensive disease and in complete ischemia of the kidney but not in the chronic
stage of the disease, the possibility exists that renin may appear in the blood as
an autolytic product of the kidney. It is also possible that renin may initiate
the pressor mechanism Avhich later proceeds without its presence.

CONCLUSIONS

Renin has not been detected in the arterial or venous plasma of tA\*enty-three
patients suffering from essential hypertension Avith and without impairment of
renal function.

TAQUINI AND FASCIOLO : RENIN IN ESSENTIAL HYPERTENSION 363

REFERENCES

1. Dell'Oro, R., and Braun-Menendez, E.; Dosaje de renina en la sangre de perros hipertensos
por isquemia renal, Rev. Soc. argent, de biol. 18; 65, 1942.

2. Leloir, L. F., MuSoz, J. M., Braun-Menendez, E., and Fasciolo, J. C.; Dosaje de la renina,
Rev, Soc. argent, de biol. 16; 635, 1940.

3. Braun-Menendez, E., Fasciolo, J. C., Leloir, L. F., Mufioz, J. M., and Taquini, A. C.;
Hipertension Arterial Nefrogena, El Ateneo, Buenos Aires, 1943.

4. Dexter, L., and Haynes, F. W.; Relation of Renin to Human Hypertension With Particular
Reference to Eclampsia, Preeclampsia and Acute Glomerulonephritis, Proc. Soc, Exper.
Biol. & Med. 55: 288, 1944.

5. Mufloz, J. M., Taquini, A. C., Braun-Menendez, E., Fasciolo, J. C., and Leloir, L. F.;
Metodo para la medicion de la renina humana, Rev. Soc. argent, de biol. 19; 321, 1943.

6. Keith, N. M., Wagener, H. P., and Barker, N. W.: Some Different Types of Essential
Hypertension: Their Course and Prognosis, Am. J. M. Sc. 197; 332, 1939.

7. Taquini, A. C., and Braun-Menendez. E.: Liberacion de renina por el riilon totalmente
isquemiado, Rev. Soc. argent, de biol. 17; 465, 1941.

8. Taquini, A. C., and Fasciolo, J. C.: Unpublished data.

9. Quinby, W C., Dexter, L., Sandmeyer, J. A., and Haynes, F. W.: The Renal Humoral
Pressor Mechanism in Man. II. The Effect of Transitory Complete Constriction of the
Human Renal Artery on Blood Pressue and on the Concentration of Renin, Hypertensinogen,
and Hypertensinase of Renal Arterial and Venous Blood, With Animal Obser\'ations, J.
Clin. Investigation 24: 69, 1945.

PARASTERNAL LEADS IN TRICUSPID INSUFFICIENCY

George M. Ellis, M.D., and N. Worth Brown, M.D.

Toledo, Ohio

T he purpose of this communication is to illustrate the electrocardiograms
of two cases presenting clinical signs of tricuspid insufficiency and right
auricular enlargement. In these cases, striking and unusual auricular deflections

of the diphasic (H ) type are found in leads from the right side of tlie pre-

cordium. Their mode of production and possible significance have been a source
of interest and speculation to us and will be discussed.

Unusual P waves in the precordial electrocardiogram have been the subject
of only a few previous papers. Burton and Mehlman’ published a report of a
case of spontaneous pneumothorax of the right side of the chest in which a deeply
inverted P wave (13 mm.) occurred in Lead CFo. Upon partial release of the
pneumothorax and during spontaneous resolution, this precordial P wave be-
came diphasic and had a configuration similar to those described in the present
report. Gertz,- also, reported a diphasic P wave in a lead taken at the C 2 position
in a case in which a calcareous tuberculous lesion of the upper left lung caused
traction on the heart. These cases differ, it will be noted, from the two we
describe in that an extracardiac factor produced displacement of the heart
toward the left and thus placed the right auricle beneath the area of the precordial
electrode. Auricular deflections of this sort have apparently not been observed
in the frequent clinical combination of cardiac decompensation with right pleural
effusion and displacement of the heart toward the left.

Pardee^ has reported two cases of uncomplicated tricuspid stenosis with
high, peaked P waves in the limb leads and discussed the findings of Winternitz
who relates the size and shape of these waves to auricular hypertrophy. Pardee
concludes that the height of the wave in limb leads is due to right auricular hyper-
, trophy, and that the notching and increased duration is due to involvement of
both auricles.

Szekely^ recently found no correlation between the size of the right auricle
and the amplitude of the P waves as recorded in chest leads taken at the third
intercostal space to the right of the sternum. He suggested as possible factors
the anatomic position of the right auricle and its juxtaposition to the anterior
chest wall.

A case of mitral stenosis and one of congenital heart disease, in which the
electrocardiograms show an auricular complex in CFi similar to those in our
cases, are illustrated by Sigler.® The P waves were large and of the diphasic

("1 ) type. Both of his cases showed right ventricular dilatation and hyper-

trophy.

From the Department of Medicine and the Heart Station of The Toledo Hospital, Toledo, Ohio.
Received for publication Dec. 24, 1945.

364

ELLIS AND BROWN : PARASTERNAL LEADS IN TRICUSPID INSUFFICIENCY 365

CASE REPORTS

^ Case 1. — D. F,, a white child, aged 12 years, was admitted to the pediatric floor of Toledo
Hospital on Nov. 3, 1945. About three weeks previously, she had had an attack of “flu” from
which she had made a satisfactory recovery. About four days prior to admission she rapidly
became edematous, dyspneic, and cyanotic.

The past history was essentially negative with the exception of pneumonia in infancy. There
had been no primary or secondary manifestations of rheumatic fever. She had been a perfectly
normal child with no evidence of congenital heart disease.

Physical examination at the time of admission revealed a well-developed and well-nourished
child, acutely and severely ill. The temperature was normal, the heart rate was 90, and the
respirations were 22 per minute. Breathing was very difficult in the semiupright position and
was accompanied by an expiratory grunt. The lips and nail beds were moderately cyanotic.
The face appeared swollen, although the eyelids were not specifically edematous. The tonsils
were hypertrophic, but the mucous membranes of the nose and throat were clear. The tongue
was dry and furrowed. The neck was puffy and flaccid. No enlargement of the thjToid gland
and no adenopathy were present. The jugular veins were not conspicuous. Examination ’bf
the lungs by percussion and ausculation revealed no changes, although the [diaphragm was
somewhat elevated on both sides.

Pig — Case 1. A-P and lateral roentgenograms.

E.xamination of the heart showed the rate to be rapid and the rhythm regular. The apical im-
pulse was displaced upward and to the left. A presj'stolic gallop and a blowing systolic murmur,
most marked at the apex, were noted. The sounds tvere very forceful. An abdominal fluid wave
and shifting dullness gave evidence of ascites. There was edema of the right labium, sacrum,
and lower e.xtrcmities. The blood pressure was 1 10/65.

Other laboratory studies showed 3-plus albuminuria, many hyaline casts, a normal red count
and hemoglobin, a leucocytosis of 32,000 with a differential of 52 segmented polys, 25 band forms,
20 mature lymphocytes, 2 monocytes, and 1 eosinophile. The nonprotein nitrogen was 57.3 mg.
per cent, and a total protein determination was 5.8 Gm. per cent with 2.5 Gm. of albumin and
3.3 Gm. of globulin '(albumin-globulin ratio; 0.76).

Paracentesis was performed, and 1,100 c.c. of cloudy, amber fluid with a specific gravity of
1.013 was withdrawn. This failed to relieve the dyspnea. Two days later her cardiac finding

rig. 2.— Case 1. Conventional leads, taken Nov. 11, 19-15. sliow'^ delayed auriculoventricular
induction time (0.^ second). Precordial leads were taken November 13. Note diphasic P waves m
kr ^ /if T^ird intercostal space to the right of the sternum. B, Third intercostal space to

oSf //’fu' 1 Second intercostal space to the right of the sternum. D, Second intercostol

Jndffferont e/^ct sternum. In these special precordial leads the loft leg uas used as the site of the

ELLIS AND BROWN : PARASTERNAL LEADS IN TRICUSPID INSUFFICIENCY 367

had become more definite, and fluoroscopic examination showed uniform pulsations of all borders
of the heart. X-ray films of the chest (Fig. i) were taken, and she was digitalized with marked
improvement.

Subsequent laboratory’ determinations revealed no albuminuria, sedimentation rates of 8
and 15 mm., improvement in plasma proteins, normal urea nitrogen, and normal blood counts.
Aright pleural effusion developed but rapidly subsided, and this was not present when the electro-
cardiograms (Fig. 2) were taken.

On November 21, the following observations were recorded: By palpation the apical impulse
is at the anterior axillary line. A short systolic thrill is felt in the left fourth intercostal space
just within the mammary line. No thrills could be felt over the pulmonic valve area or in the neck
over the carotids. There is a loud systolic murmur over the precordium. This murmer is loudest
in the mitral area but is transmitted into the infra-axillary space, and posteriorly to the sub-
scapular area. Systolic and diastolic murmurs are heard in the aortic area and down the left
border of the sternum. Systolic and diastolic murmurs are heard in the tricuspid area also.
The latter murmers blended with the dominant murmurs, but because of the enlargement of the
liver and its expansile systolic pulsation, were believed to be of tricuspid origin.

The diagnostic impressions were: (1) aortic regurgitation with possibly some stenosis,
(2) mitral regurgitation with possibly some stenosis, and (3) tricuspid regurgitation. The lesions
were evidently the result of a recent carditis involving chiefly the aortic and mitral valves com-
plicated by a relative tricuspid insufficiency.

Case 2. — S. W. J. was an 18-month-old boy. The history as related by the parents told of
a normal delivery with no physical defects discovered by the attending physician. No respiratory
disturbance nor cyanosis was noticed by the family. At the age of 9 months the child contracted
a severe throat infection which necessitated three weeks’ hospitalization. After discharge, he
suffered a relapse with pulmonary complications. At this time his physician noticed a loud heart
murmur which is said to have gradually increased in intensity during and after this illness. Six
months ago another physician made the diagnosis of congenital heart disease, which was substan-
tiated with frontal and lateral x-ray films.

On Nov, 11, 1945, the child was examined at the Toledo Clinic. At that time he appeared
healthy and well nourished but somewhat backward in both physical and mental development.
The chest was of normal shape and symmetrical. There was a large, diffuse impulse visible over
the precordium, with the point of maximal intensity in the anterior axillary line. By percussion
the right border was 3 to 4 cm. to the right of the sternal margin; the right costophrenic angle
was not obliterated. There were no thrills over the precordium or carotids. The liver was of
normal size, and the spleen could not be palpated. A long, loud, and rather harsh systolic murmur
could be heard over the precordium and was well transmitted into the axilla and also heard pos-
teriorly in the interscapular space. There was also a systolic and -early, high-pitched, diastolic
murmur of an entirely different tonal quality which was localized to a relatively small area over
the lower sternum and the left fourth and fifth intercostal spaces. There was no presystolic
element connected with any of these murmurs. During inspiration there was a reduplication
of the second sound which was heard best in the second left intercostal space. The pulse rate at
the time of the examination was 130 per minute. Arterial pulsation could easily be felt in the
popliteal space. The hemoglobin was 96 per cent (Sahli), the red cell count was 5,310,000, and
the leucocj^tes numbered 16,150. A single blood culture was negative. Frontal and lateral x-ray
films showed a large globular heart (Fig. 3). The most conspicuous feature was the enlargement
of the right auricle and right ventricle. The roentgenogram supported the clinical diagnosis of a
congenital heart, the chief lesion being an interventricular septal defect. The electrocardiogram
is illustrated in Fig. 3.

It seemed probable that the localized, high-pitched murmur was due to a relative tricuspid
insufficiency. Although no enlargement of the liver could be demonstrated, x-ray films showed
enlargement of both the right auricle and right ventricle so clearly that relative insufficiency of
the tricuspid valve was considered a proper assumption.

Fig 3 — Case 2 A,-P and lateral (o2 inch) roentgenograms. Conventional loads, tall, peaketi P naves

in I and IT, QRS complevcs of large amplitude Mote diphasic P n-a\o in CPi

DISCUSSION

Attention is directed to the auricular deflections in Lead CFi of both cases.
They consist of large, diphasic (+ — ) waves with a sharp transition between
the positive and negative components (Fig. 4).

These large, diphasic P waves are strikingly similar to auricular complexes
seen in esophageal leads. They are also similar in contour to the P waves ob-

I

ELLIS AND BROWN : PARASTERNAL LEADS IN TRICUSPID INSUFFICIENCY 369

tained by Lewis® and Wilson, Macleod, and Barker’ when an electrode was placed
on the exposed auricle of a dog. As the peak of maximum positivity of the
auricular complex represents the arrival of the excitation wave directly beneath
the exploring electrode, we attempted in Case 1 to obtain varying proportions
of positivity and negativity by taking parasternal leads from the third and
second intercostal spaces; that is, from points nearer to the sinoauricular node.
These are illustrated in Fig. 2.

From the character of the auricular complex in Case 2, it would seem that
the electrode must have been so placed on the chest as to be in close proximity
to the upper portion of the right auricle and not far from the sinoauricular node.
This would account for the small initial positivity, the early downward stroke,
and the prominent negative component.

A. B. C.

Pjg. 4 — Photographic enlargements illustrating the size and shape of the auricular complexes in Lead
CFi. A, Case 1; li. Case 2; G, Lead OFi in normal ll-year-old child for comparison.

SUMMARY

Two cases are presented with clinical and x-ray findings of hypertrophy
and dilatation of the right ventricle and right auricle, associated with tricuspid
insufficiency. The electrocardiograms show large, diphasic P waves in Lead
CFi such as are normally obtained from esophageal leads and experimentally
in direct leads from exposed auricles. It is probable that the proximity of the
enlarged right auricle to the anterior chest wall is largely responsible for an auricu-
lar wave of this type. Further observations may show that, in tricuspid insuf-
ficiency and right auricular enlargement, this characteristic auricular complex
in parasternal leads is a significant diagnostic sign.

REFERENCES

1. Burton, S. D., and Mehlman, J. S.; An Unusual P Wave in Chest Lead CFj. Following
Spontaneous Pneumothorax, J. Lab. & Clin. Med. 27; 465, 1942.

2. Gerta, G. F.: An Unusual P Wave in Lead IV, Am. He.\rt J. 15; 498, 1938.

3 . Pardee, H. E. B.: Clinical Aspects of the Electrocardiogram, ed. 4, New York, 1941, Paul
B. Hoeber, Inc., pp. 77-80.

4' Szekely, P.: Chest Leads for the Demonstration of Auricular Activit 3 % Brit. Heart J.
6 : 238, 1944.

5. Sigler, L. H.: The Electrocardiogram, New York, 1944, Grune and Stratton, Inc., p. 380.

6. Lewis', T.; Lectures on the Heart, New York, 1915, Paul B. Hoeber, Inc., pp. 8-16 and Fig. 9.

7. Wilson, F. N., Macleod, A. G., and Barker, P. S.: The Distribution of Currents of Action
and Injur\’ Displayed by Heart Muscle and Other Excitable Tissue, Ann Arbor, 1933,
Univ. Mich. Press, pp. 8-12 and Fig. 3.

PERSISTENCE OF THE JUVENILE PATTERN IN THE PRECORDIAL
LEADS OF HEALTHY ADULT NEGROES, WITH REPORT OF
ELECTROCARDIOGRAPHIC SURVEY ON THREE HUNDRED
NEGRO AND TWO HUNDRED WHITE SUBJECTS

Captain David Littmann, M.C.

Army of the United States

T he genesis of the T wave in the normal electrocardiogram is still somewhat
of a moot point. Irrespective, however, of whether the T wave is the result
of organized electrical regression in the ventricles or of the geometric inequality
of the complexes derived from the left and the right ventricles, most observ^ers
are in agreement that it is upright in electrocardiograms derived from the left
side of the chest in adults.^ The literature contains numerous excellent surveys
on large groups of normal individuals which confirm this observation; a few of
these will be reviewed briefly.

In 1936, Shipley and Halloran^ examined the electrocardiograms of 200
normal men and women between the ages of 20 and 35 years and noted that
T4 Avas inverted in all instances.* Skulasen and Larsen® made a similar study
of patients between 30 and 50 years of age and found that the T waves from the
chest leads were consistently upright. Wood, Wolferth, and Miller'* studied 299
college students and found three diphasic and one inverted T4. The latter was
in a young man with aortic insufficiency; all the other subjects were normal.
In a similar manner, Graybiel and his co-workers® made five-lead electrocardio-
grams (Leads I, II, III, IV F, and IV R) on 1,000 healthy aviators and noted
two diphasic T waves in Lead CF4 and none in Lead CRj. There were no nega-
tive T waves.

When the use of chest leads became common, it was soon apparent that in
children the T waves derived from the left side of the chest ivere very frequently
’ opposite in direction to those obtained from similar positions in adults. The
cause of this phenomenon has been studied extensively by various investigators.
Since much of this work was done by the old technique in which the adult T4
is normally inverted, it will be less confusing if we employ wherever possible,
and at least during this phase of the discussion, the terms juvenile and adult
rather than inverted and upright waves.

Rosenblum and Sampson® studied 66 adults and 50 children and noted
abnormal T waves in three of the adults. One was in a 16-year-old girl; the other
two diverged only slightly from normal. Two of the 50 children demonstrated
adult patterns and these were in subjects aged 14j4 and 15 years. Dwan and

Heceived for publication Jan. 19, 1946. , „ ,

♦When tills study was made, the technique used was such that an inverted T 4 'vas normal.

370

LITTMANN : PERSISTENCE OF JUVENILE PATTERN IN PRECORDIAL LEADS 371

Shapiro^ studied several hundred children with normal and diseased hearts.
They reported a high incidence of the juvenile form and, among other conclusions,
stated that the findings in routine four-lead electrocardiograms appeared to be
constant from day to day. Deeds and Barnes,® who e.xamined 50 normal men and
a similar group of women, found one subject in whom, the T wave in Lead CR2
approached negativity, while in the other precordial positions the T wave was
positive. The}'^ concluded that the juvenile form in subjects older than 15
years was to be considered abnormal. Master, Dack, and Jaffe® noted juvenile
electrocardiograms in 60 per cent of a group of children between the ages of 2
and 15 years. Only 5 per cent of juvenile patterns appeared in the group
between 11 and 15 years of age. They suggested that the difference between
the adult and juvenile forms was the result of earlier predominance of the right
ventricle and of the normally greater relative anteroposterior diameter of the
chest in children.

Robinow, Katz, and Bohning^® noted that juvenile patterns were more
frequently found in children who had a thin chest wall and narrow thorax and
less commonL^ in those with a more nearly adult type of chest. They made an
exhaustive study of the problem and suggested reasons for the differences noted
between adult and juvenile tracings. The known physical differences considered
in their paper included the relative right ventricular predominance and axis
rotation, the tendency for the heart to lie more horizontally, the greater pro-
portion of the right ventricle lying in the area of left precordial dullness, and
the more intimate contact of the heart with the chest wall. All of these are
present in childhood. Since the configuration of the tracing is thought to be
dependent, to a large extent, upon the conductivity of the tissues interposed
between the heart "and the chest wall, and since the chest electrode is placed in
relation to the bony framework, it does not, therefore, bear the same relation
to the heart in children as it does in adults.

The authors suggested that “The variations of T4 in normal different chil-
dren could be explained on the variable degrees of transition from the ‘puerile’
to ‘adult’ chest type.” The same observ^ers also studied electrocardiograms
obtained from 20 normal children after a lapse of six to eight months and noted
changes toward the adult form in seven instances and away from it in three.

Thus far, reasonable evidence has been obtained from the literature that
in adults the T waves in leads derived from the left side of the precordium are
normally upright, while in children they are frequently inverted. The theories
advanced in explanation of this phenomenon are concerned largely with the
differences between adult and juvenile hearts and chests, and the resultant
change in relationship of the heart to the chest wall and exploring electrode.
However, a number of instances of T4 abnormality in adults with and without
evidence of heart disease have also been noted.

Edeiken, Wolferth, and Wood” noted 26 instances of abnormal T4 in adults
in whom the other leads were normal. All of their patients, however, had some
type of organic disease. They felt that an abnormal T4 should not be disregarded
and should be an indication for additional study for evidence of heart disease.

372

AMERICAN HEART JOURNAL

They concluded that they had not yet seen an abnormal T 4 in an adult in whom
they were confident that “there was no significant heart disease.’’

Sodeman^- reported an instance of a reversal of T 4 in a 26-year-old nurse
without other evidence of disease. Shanno*'"’ recorded his observations on electro-
cardiograms of 100 student nurses, aged 18 to 22 years. There were si.\ instances
of T-wave negativity in Lead CF 2 , one in Lead CFs and none in Lead CF4. No
explanation was offered by either Shanno or Sodeman for these anomalies.
Pardee, who observed occasional abnormalities in one chest lead, recommended
the use of multiple leads and further observation in such cases.

Dupuy^® reported five cases of T-wave abnormalities in apparently normal
soldiers. Several had T 4 changes, but these were invariably associated with
abnormalities in Ti and Ta and occurred in individuals who had some type of
cardiovascular complaint. Some of the tracings were grossly abnormal but
were considered to be functional variants because they were reversible following
rest and sedation. He suggested that these variants might be due to cardiac
rotation or to anxiety associated with a rapid cardiac rate.

Thompson'® described interesting electrocardiographic changes which
occurred during hyperventilation in susceptible individuals. Here, too, altera-
tions were observed in the T waves of any or all leads in subjects with anxiety
neuroses, precordial pain, tachycardia, and hyperventilation. This was con-
sidered to be the result of associated alkalosis. It is not improbable, however,
that the anomalies recorded by both Dupuy'® and Thompson'® during anxiety,
tachycardia, and hj'^perventilation were in some manner associated with coronary
vasoconstriction in preclinical heart disease. Thompson considered this possi-
bility.

In a similar manner Katz" and McGuire'® have observed reversible T-wave
changes in nervous individuals. Graybiel, Starr, and White'® have also noted
S-T interval and T-wave changes resulting from the inhalation of tobacco smoke.
The T-wave inversions following the ingestion of ice water are well known.

On the whole, however, the number of adults exhibiting T-wave inversion
in the precordial leads in the absence of demonstrable heart disease is compara-
tively small.

In reviewing over 3,000 electrocardiograms made during a one-year period
at an Army installation, a small number of T 4 inversions was noted. But, with
three exceptions, these were all associated with organic disease of the heart
and/or pericardium or occurred during the course of acute rheumatic fever.
The three exceptions were extensively studied, but no evidence of heart disease
was ever demonstrated. All three exceptions were in Negroes. This observation
suggested a preponderance of the anomaly among Negroes, and since a review
of the literature failed to reveal any large scale study of electrocardiograms of
normal adult or juvenile Negroes, such a survey was undertaken.

MATERIAL AND METHODS

The instruments used in this study were Sanborn cardiettes which were
frequently calibrated and compared. All tracings were made with the subject

Table I. Physical Description, Mistory, and Laboratory Findings in Subjects Who Demonstrated 'Pi Abnormality

LITTMANN ;

PERSISTENCE OF JUVENILE PATTERN IN PRECORDIAL LEADS 373

physical

examination

Negative

Negative

Negative

Negative

Negative

Negative

Soft syst iic
basal murmur
Soft systolic
basal murmur
Negative
Negative
Negative

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374

AMERICAN HEART JOURNAL

lying down on a padded wooden table. Occasionally, when abnormalities were
observed, the electrocardiogram was repeated in the erect position. Particular
care was taken in the recording and development of the tracings, and most of
this was done by the author. All of the subjects were adults between the ages
of 18 and 35 years. There were 200 Negro men, 100 Negro Avomen, 100 white
men, and 100 white women. They were picked from the normal active personnel
of an Army post, and no hospital patients were included. No one was included
who had had a recent illness, a history of gonorrhea or syphilitic infection, or any
complaints referable to the cardiovascular system. All subjects were told about
the study in a general waj' and were reassured before the electrocardiograms
were made. Each was rested for ten minutes to one hour. When asked to return
for additional studies, they were once more assured that no heart disease Avas
present and that they had no cause for concern.

Routine four-lead electrocardiograms (Leads I, II, III, and IV F) Avere
made and examined. All subjects Avho shoAved any degree of T 4 inversion Avere
requested to return for further testing. At this time, a careful history AA'as
obtained Avith particular reference to rheumatic fcA'er, scarlet fev'er, recent
pharyngitis, cardioA'ascular symptoms, and the use of any drugs. The tempera-
ture, AA’^eight, and height AA'ere recorded. The blood pressure A\'as measured, and
the heart AA^as carefullj^ examined. The folIoAving additional studies AA'ere ob-
tained: (1) teleroentgenogram of (he chest, (2) hemoglobin, (3) Kahn reaction,
(4) examination of the blood film for sickling, and (5) sedimentation rate. An-
other electrocardiogram AA’as then made, employing, in addition to the original
four leads, the six standard precordial leads Avith the indifferent electrode on
the left leg. In some cases Leads IV R, IV L, and IV V Avere also recorded.

Table I summarizes the physical descriptions and laboratory findings in
those subjects Avho shoAA’’ed T-Avave abnormalities and Avere studied sufficiently
to be included. Three subjects AA'-ere omitted from this list because of incomplete
records.

RESULTS

The results of this study are summarized in Table 11. It aauII be noted that,
of the 300 Negroes studied, 4.6 per cent had tracings Avhich Avould be considered
abnormal. The AA’^omen had a much larger incidence of T-AA^ave abnormality:
4 per cent AA^ere diphasic, and 4 per cent AA'ere inverted. All of the abnormal
tracings obtained from the AA’'omen are reproduced in Figs. 1 and 2. The incidence
of T-Avave changes in the precordial leads of Negro men Avas 3 per cent Avhile
1 per cent had frankly abnormal curA^es. The latter are reproduced in Figs.
3 and 4; those shoAving merely diphasic T AA’^aves are not shoAvn. An
electrocardiogram Avas obtained from one A\ffiite man in Avhich the T Avaves in
the precordial leads AA^ere diphasic Avith the negath^e portion 0.5 mm. in depth.
There Avere no abnormal tracings among the Avhite Avomen.

Table III is a summarized analysis of the records. Since it is not apparent
from the tracings shoAvn, it is AA'^ell to add that the heart rates varied betAA^een
64 and 90 and there AA’-ere no instances of abnormal arrhythmia. Several general
impressions are possible from examination of the electrocardiograms. There

LITTMANN ;

PERSISTENCE OF JUVENILE PATTERN IN PRECORDIAL LEADS

375

were no instances of abnormality of any portions of the curves derived from the
limb leads. The axis varied between -T33 and +103, i. e., normal to very slight
right axis deviation; no instance of left axis deviation was noted. Ti and To
were always upright and an inverse relationship apparently existed between
Ta and T 4 ; the greater the height of Ta, the greater the depth of T 4 . T 3 was never
frankly inverted but was flat in two instances and diphasic in one. All of the
precordial T waves were diphasic or negative from Lead .CFa through Lead CF4;
Leads CFi and CFa usually had the greatest negativity and Lead CF4 .had the
least. In some instances, inversion was present in Lead CFe and even in CFe,
but, for the most part, the T waves in Leads CFs and CFg were upright. Where
Lead CR (IV R) was made, the T waves were usually but not invariably upright.
Leads IV L and IV V were variable.

Table II. Summary of the Frequency of Abnormal Precordial T Waves in 300

Adult Negro and 200 White Subjects

Negro, both sexes (300)

Normal curves

Diphasic T 4

Inverted T 4

Negro men (200)

Normal curves

Diphasic T 4

Inverted T 4

Negro Women (100)

Normal curves

Diphasic T 4

Inverted T 4

Whites, both sexes (200)

Normal curves

Diphasic T 4

Inverted T 4

White men (100)

Normal curves

Diphasic T 4

White Women (100)

Normal curves

286 95.34%

8 2 . 66 %

6 2 . 00 %

194

4

2

92

4

4

199

99.5%

1

00.5%

0

00 . 0 %

99

1

100

Approximately two months after the original tracings were obtained, those
subjects who exhibited electrocardiographic abnormalities were requested to return
for additional studies. All of the women and four of the men were reached, but the
remainder had left the post and could not be re-examined. Of the electrocardio-
grams which were reported, six remained unchanged (5 and C in Fig. 1, G and H
in Fig. 2, Fig. 3, and one electrocardiogram not shown). A in Fig. 1 had become
entirely normal. D retained an inverted T wave in Lead CFo but the T wave
in Lead CF3 had become diphasic and that in Lead CF4 had become upright.

, In E, the T wave in Lead CF5 became upright and in Leads CFs and CF4 it was
diphasic with Lead CFs unchanged. In E, the T wave in Lea.d CF4 became posi-
tive, in Lead CFs it became flat, and in Lead CF2 there was no change. One of
the tracings, that of a Negro man, which demonstrated diphasic T waves, became

Atiiiornial cIcctrocarilloKrams of live Xfv^ro woinoa.

Table III. Summary of I^cord Analysis’

littmann:

PERSISTENCE OF JUVENILE PATTERN IN PRECORDIAL LEADS 379

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380

AMERICAN HEART JOURNAL

entirely normal while another developed frankly inverted T waves. It would
appear, therefore, that when changes in the direction of normal become manifest
they do so first in those leads farthest from the sternum. In addition, it is
probable that changes may occur either toward or away from the normal pattern.

DISCUSSION

The size of the group being studied is too small for detailed statistical con-
clusions. However, certain facts are evident. T wave inversion in the precordial
leads is far more common among normal adult Negroes than among white sub-
jects and is apparently more frequent in Negro women than in Negro men. In
no case here reported was there any cardiovascular complaint or any demonstrable
evidence of organic or functional disease of the heart. None of the subjects had
any active or recent infection. The abnormalities were noted in a group of
healthy, confident, young men and women who had not been smoking, taking
drugs, drinking cold water, or hyperventilating.

In a general way, it is noted that in the cases reported in this study, the
heart tended to be relatively sm.all and there were no instances of enlargem.ent.
Similarly, the electrical axis fell toward the right and was never rotated to the
left. Although a few of the women were rather stout, none was obese and most
of the chests were thin. The men, particularly, were thin chested. These
observations tend to confirm the impression of juvenile chest configuration in
these individuals.

In the literature reviewed it is probable that the studies were carried out
on white subjects. References to electrocardiographic studies on the Negro are
limited. Laws,^” in a discussion of the etiologj'^ of heart disease in the Negro,
concludes that “The Negro develops heart disease at an earlier age, on the
average, than the white.” Is it likely that the Negro subjects under discussion
were demonstrating the first evidence of organic heart disease? Observations
incident to the present study argue against such a conclusion. It is also thought
that certain .degenerative cardiac conditions, angina pectoris, for example,
occur less frequently in Negro than in white subjects. Weiss-* has reported,
however, that angina in Negroes is fairly common. Ashman,-- who made an
electrocardiographic stud}' of Caucasians and Negroes, reported no unusual inci-
dence of T-wave abnormality. Furthermore, all of his subjects were over 30
years of age and the data were obtained from hospital records. Presumably,
these were all cardiac patients since there was a high incidence of organic heart
disease.

Apparent inadequacies of the literature are noted. At the present time,
no comparative studies can be found on white and Negro children. It is known
that most white children have acquired an upright T wave in the chest lead by
the age of 15 years. Can the same be said about the Negro? Comparatively
few studies have been recorded regarding the manner in which the T wave
becomes upright during adolescence. Does it become positive first in the fifth
or sixth precordial position, as seems probable, or are the changes first apparent
in other positions? Is the progress from the negative to the positive direction

LITTMANiSr: PERSISTENCE OF JUVENILE PATTERN IN PRECORDIAL LEADS 381

constant and steady, or is it subject to frequent recessions? The work of Robi-
now and his associatesl" suggests that the latter is actually the case.

It is possible that not all cases of T4 inversion in the group herein reported
were due to the same cause. It will be recalled that of 12 subjects who were re-
examined after approximately ten weeks, five showed changes toward the normal.
It would be altogether too fortuitous to expect that so high a proportion should
have chosen the same time to acquire adult characteristics. However, since it is
uncertain that the erection of a juvenile T wave is a continuous" progression and
not an unsteady equilibrium, that possibility must be considered. Unfortu-
nately, because of the constantly changing character of the personnel on an Army
post, it was not possible to repeat the studies on the same group.

There exists, therefore, an apparent abnormality, possibly transient or
shifting in character, in a very appreciable percentage of young and presumably
healthy Negro men and women. It is more common in women than in men and
apparently occurs very rarely in white subjects. It is associated with suggestive
juvenile characteristics. Women -s chests are normally less broad from side to
side than men-s and this may account for the higher incidence observed in the
female sex.

These findings were noted in the complete Absence of symptoms or signs
of organic or functional heart disease. In a similar manner, there was no evi-
dence of current or recent infection, rheumatic fever, drugs, syphilis, anemia, or
sickling of erythrocytes. The reasons noted and the exclusion of other known
causes of such anomalies lead to the conclusion that the T-wave inversion in
the chest leads of otherwise normal adults constitutes a persistence of the juvenile
pattern and should be considered a normal variant.

Since this anomaly is manifested more frequently when the left leg rather
than the right arm is employed for the indifferent electrode, it is desirable that
the study be repeated using various indifferent connections. Electrocardiograms
should also be made over a prolonged period of time, as the phenomenon appar-
ently disappears with the passage of time.

Much additional study of the electrocardiograms of youthful white and
Negro subjects will be required before a satisfactory explanation of this apparent
anomaly can be made. At the present time, there seems to be no adequate
reason for the greater frequently of juvenile electrocardiograms in adult Negroes
than in adult white subjects.

SUMMARY

1. In an electrocardiographic survey of 500 healthy adults, 300 Negro and
200 white subjects, diphasic or inverted T waves in the precordial leads were
observed in 14 Negroes, eight among 100 women and six among 200 men. Among
white subjects a diphasic T wave was noted in only one instance.

,2. It is suggested that the presence of diphasic or inverted T waves in the
precordial leads under the circumstances constituted a persistence of the juvenile
pattern and was not a manifestation of organic heart disease.

382

AMERICAN HEART JOURNAl.

REFERENCES

1. Joint Recommendations of tlie American Heart Association and Cardiac Society of Great
Britain and Ireland. Standardization of Precordial Leads, Am. Hkart J. 1.5: 107, 1938.

2. Shipley, R. A., and Halloran, W. R.; The Four Lead Electrocardiogram in 200 Normal
Men and Women, Am. Hkaht J. 11; 325, 1936.

3. Skulasen, T. and Larsen, K.; The Normal Electrocardiogram, Am. Heart J. 22: 645, 1941.

4. Wood, C. F., Wolferth, C. C., and Miller, T. G.: Electrocardiography in Militarj- Medicine
With Special Reference to Its Lack of Value in the Study of Recruits, War ^Icd. 1 : 696, 1941.

5. Graybiel, A., McFarland, R. A., Gates, D. C., and Webster, F. A.: Analysis of the Electro-
cardiograms Cbtained From 1,000 Young Healthy Aviators, Am. Heart j. 27: 524, 1944.

6. Rosenblum, H., and Sampson, J. K.; The Study of Lead IV of the Electrocardiogram in
Children With Special Reference to the Direction of the Excursion of the T Wave, A.m.
Heart J. 11: 49, 1936.

7. Dwan, P. F., and Shapiro, W. J.: The Four Lead Electrocardiogram of Children, Am. J.
Dis. Child. 54: 265, 1937.

8. Deeds, D., and Barnes, A. R.; The Characteristics of the Chest Lead Electrocardiograms
of 100 Normal Adults, Am. Heart J. 20: 261, 1940.

9. Master, A. M., Dack, S., and JafTe, H. L.: The Prccordiogram of Normal Children, Am. 1.
Dis. Child. 53: 1000, 1937.

10. Robinow, M., Katz, L. N., and Bohning, A.: The .Appearance of the T-Wavein Lead IV
in Normal Children and in Children With Rheumatic Heart Disease, Aji. Heart J. 12:
88, 1936.

11. Edeiken, J., Wolferth, C. C., and Wood, F. C.: The Significance of an Upright or Diphasic
T-Wave in Lead IV When It Is the Only Definite Abnormality of the Adult Electrocardio-
gram, Am. Heart J. 12: 666, 1936.

12. Sodeman, W. A.; The Occurrence of an Upright T-Wave in Lciid IV in a Patient Without
Other Ev'idence of Heart Disease, Am. Heart J. 11: 367, 1937.

13. Shanno, R. L.; Variations in Normal Precordial Electrocardiograms. A Report of Obser-
vation on 100 Normal Subjects, Am. Heart J. 19: 713, 1940.

14. Pardee, H. L.; Electrooirdiograms With Normal Limb Leads and With Abnormality in
Only One of Four Procordial Lciuls. J. Mt. Sinai Hosp. H: 898, 1942.

15. Dupuy, H.; Norma! Variations of the T-Wave Seen Among Armv Soldiers, New Orleans
M. & S. J. 96: 239, 1943.

16. Thompson, P.: The Electrocardiogram in the Hyperventilation Syndrome, Am. Heart
J. 25: 372, 1943.

17. Katz, L. N.: Lecture Before American College of Physicians, November, 1944.

18. McGuire, J.: Persona! communication.

19. Graybiel, A., Starr, R. S., and White, P. D.: Electrocardiographic Changes Following
Inhalation of Tobacco Smoke, Am. Heart J. 15; 89, 1938.

20. Laws, C. L.; The Eliologv of Heart Disease in Whites and Negroes in Tennessee, A^t.
Heart J. 8; 608, 1933.

21. Weiss, M. M.: The Problem of Angina Pectoris in the Negro, Am. Heart J. 17: 711, 1939.

22. Ashman, R.: An Electrocardiographic Study of Caucasians and Negroes, Tri-State M. J.
13: 2686, 1941.

ELECTROCARDIOGRAPHIC CHANGES OCCURRING' DURING
UPPER RESPIRATORY INFECTIONS

Major Dennison Young, Medical Corps, Army of the United States

TT IS becoiriing increasingly apparent that transient or permanent cardiac
involvement as a result of a toxic state or direct bacterial or viral invasion
may be a concomitant of many infectious diseases. The following report is
presented to demonstrate cardiac susceptibility in the course of mild, apparently
benign upper respiratory infection, in many instances with no bacteriologic
evidence of pathogenic microorganisms in the nasopharyngeal secretions.

material and methods

The thirteen patients presented in this series were all military personnel,
hospitalized because of respiratory infection. Cultures were made routinely
from swabbings of the nasopharynx. Serial electrocardiograms at t^vo- or
three-day intervals, usually starting on the day after admission, and repeated
cardiac fluoroscopic and clinical examinations were made.

results

The clinical and laboratory data are shown in Table I. Of the thirteen
cases, Group A beta hemolytic streptococci were present in nasopharyngeal
cultures in only five. Only one type was recovered on repeated culture from
each of these five cases. In one case a Group B and in one a Group G beta
hemolytic streptococcus was isolated. In six cases, a beta hemolytic streptococcus
was at no time discovered in the nasopharynx, repeated cultures showing only
the usual nasopharyngeal organisms.

The most frequent electrocardiographic changes obtained were T-wave
inversions and depressions. These occurred as the only change in seven cases.
Four patients developed auriculoventricular conduction disturbances with
prolongation of the P-R interval from 0.04 to 0.05 second beyond the normal
duration. One additional patient showed marked T-wave changes and an inter-
mittent A-V nodal rhythm. One patient also showed a widening of the QRS
complex and runs of A-'V nodal tachycardia. T-wave changes and the variation
of the P-R interval cannot be ascribed to postural effects, for all electrocardiograms
.were taken with the patients in the recumbent position.

Clinically, except for Case 5, these patients were not acutely ill on admission
nor during their period of hospitalization. There was no essential difference in
the severity or duration of the acute phase between those with a hemolytic

Rccoivecl for publication Feb. 23, 1940.

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Acute tonsillitis Ti, +0.5 to +2.0 8 10 Group A, 15,200, P 92 Received 15 Gm. sul-

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386

AiSrERICAN HEART JOURNAL

streptococcal infection of the throat and those with a simple nasopharyngitis.
A leucocytosis was present in three of the patients with Group A infection but
in none of the others. The erythrocyte sedimentation rate was not elevated in
all cases. Two of the patients with Group A hemolytic streptococci in the naso-
pharynx clinically and hematologically had infectious mononucleosis.

None of these patients had a past history suggestive of rheumatic fever.
None showed clinical or fluoroscopic evidence of pre-existing cardiac disease nor
did they develop any clinical signs or symptoms of heart disease, other than
the electrocardiographic changes, during the period of observation. There was
no laboratory evidence of a renewed acti\'e infectious process during the period
that electrocardiographic changes were present.

Only one patient developed clinical manifestations suggesting rheumatic
fever (Case 10). This patient suffered from fairly severe arthralgias for one week
during his illness, but there were no objective signs of joint involvement. He
had a typical infectious mononucleosis with a heterophile agglutination titer of
1:3,584.

In a fruitless attempt to eliminate the hemolytic streptococcus from the
nasopharynx, five patients in this series (Table I, Cases 1, 5, 6, 7, and 13) were
given sulfadiazine in varjdng doses. In these five the drug was started two,
twenty-eight, one, four, and ten daj's, respectively, prior to the first electro-
cardiographic indication of myocardial involvement. All other patients received
only symptomatic treatment during the acute phase.

CASE REPORTS

Case 1. — This case is of considerable interest in that the patient was hospitalized twice with
acute tonsillitis and on each admission developed electrocardiographic changes despite a distinct
difference in the nasopharyngeal cultures. The first admission was because of a progressively
severe sore throat of one week's duration. The oral temperature was 101° F. and c.\amination
revealed diffuse injection of the pharjmx; the tonsils were large and inflamed. The throat culture
showed no unusual organisms. Treatment was entirely symptomatic. Signs and symptoms
rapidly subsided and the temperature returned to normal on the fifth hospital day. Electro-
cardiographic e\idence of myocardial involvement, manifested by low T waves in Leads I and
II and inversion of the T wave in Lead III, appeared on the nineteenth day of illness. Three
days later the tracing had returned to normal (Fig. 1, A and B).

The patient was well at time of discharge from the hospital and remained so until five months
later when he was readmitted because of sore throat, malaise, and fever of one day’s duration.
The tonsils were large, reddened, and covered with e.xudate. The oral temperature was 103° F.
and remained elevated for the first four hospital days. Throat culture revealed a Group A beta
hemolytic streptococcus which was not typablc. On the fifth day of illness, significant changes
were present in the T waves of the electrocardiogram. These changes became progressively
more marked, and the tracing did not return to normal until forty-one days later (Fig. 1, C, D,
and E). During this period the patient was objectively and subjectively well; laboratorj' data
revealed no evidence of infection after the tonsillitis had subsided. Subsequent follow-up for
two months after discharge from the hospital revealed no clinical or laboratory abnormalities.

after onset of acute nasopharyngitis.

YOUNG: ECG CHANGES AND UPPER RESPIRATORY INFECTIONS

389

Two other cases illustrating the development of marked electrocardiographic
changes early in the course of simple upper respiratory infections are presented.

Case 3. — W. C. was hospitalized because of cough, fever, and chilliness of two days’ dunation.
The temperature was 100° F. orally on admission, and although the patient appeared moderately
ill, the onh' abnormal finding was congestion of the nasal mucosa. Laboratory data were normal.
Repeated nasopharyngeal cultures failed to show any unusual organisms. The patient was
afebrile after the first hospital day and all signs and symptoms were gone in four days. .At no
time was there a leucocytosis or elevation of the erjThrocyte sedimentation rate. During a five-
month period of observation he displa3'ed no clinical cardiovascular signs or symptoms.

The electrocardiogram on the fifth da\' of illness revealed an almost isoelectric T wave in
Lead I and an inverted T wave in Lead IV (Fig. 2, A and B). Twenty days later Ti measured
1 mm. and T4 was slightlj’’ upright (Fig. 2. C). The first normal tracing was obtained eightj*-
three day's after the onset of the upper respiratory' infection (Fig. 2, D) ; subsequent electrocardio-
grams showed no further change.

C.A.SE 9. — S. C., an T8-year-old soldier, was admitted to the hospital because of a slight non-
productive cough and sore throat of three day's’ duration. Examination revealed moderate swel-
ling and redness of the tonsils with flecks of white exudate on the surface. The patient was not
acutely ill and was afebrile on admission and remained so throughout his hospital stay. The acute
manifestations subsided in three days.

Laboratory' data were normal and did not change significantly' during the period of hospitali-
zation. A Group G beta hemoly'tic streptococcus was obtained on initial throat culture and was
present on repreated nasopharyngeal swabbings. No other beta hemolytic streptococci were
obtained.

The electrocardiogram taken ten day's after the onset of the patient’s upper respiratory in-
fection showed a deeply inverted T wave in the fourth lead. Two day's later Ti was upright but
the T waves in the first three leads were distinctly' lower. One week later the T waves were
normal in all leads and subsequent follow-up studies revealed no change (Fig. 3, A, B, and C).

A. li. ■ c.

Pjg. 3. — Case 9. Electrocardiograms A, B, and C taken ten. Dvelvo, and nineteen
days, respectively, after onset of acute tonsillitis.

390

AMERICAN HEART JOURNAL

DISCUSSION

The electrocardiographic changes found in these thirteen patients are un-
equivocal evidence of myocardial involvement. Since all patients recovered, the
exact pathologic significance of the electrocardiographic changes can only be sur-
mised. Candel and Wheelock^ recently reported a case of sudden death in a
patient with acute suppurative tonsillitis from whom throat cultures had shown
a beta hemolytic streptococcus (not grouped). Microscopically the myocardium
showed pronounced fragmentation of the bundles with loss of cross striations,
disintegration of muscle nuclei, interstitial edema, and a widespread diffuse in-
filtration of the interstitial tissue by polymorphonuclear cells. This apparently
is the first recorded post-mortem report of acute nonspecific myocarditis
following acute tonsillitis, although Schultz,® in 1937, recorded a case of sudden
death in a 21-year-old soldier in whom autopsy revealed a- diffuse interstitial
myocarditis believed to have been secondary to tonsillar infection.

Several authors have reported electrocardiographic evidence of acute myo-
carditis following tonsillitis. Scherf® demonstrated five such cases and indicated
that from 10 to 15 per cent of patients with acute tonsillitis develop signs, symp-
toms, or changes in the electrocardiogram suggesting myocardial involvement.
Carr and Walsh" and Maher and Wosika® have also recorded electrocardiographic
changes with tonsillar infection. In their paper on acute nonspecific myocarditis,
Candel and Wheeloclc® included a case of peritonsillar abscess and one of infectious
mononucleosis.

It is quite possible that electrocardiographic changes occur in much greater
frequency in all respiratory infections than has been previously recognized.
Scherf and Boyd® suggest that with the frequency of infectious diseases and mis-
cellaneous infections such as tonsillitis, there are but few individuals who at some
time do not have small inflammatory myocardial foci. To date, however, since
no serial electrocardiographic study has been made in a large series of patients
with upper respiratory infection, an accurate statistical incidence of evidence of
cardiac involvement in this type of illness has not been obtained.

Unfortunately the bacteriologic findings in the nasopharynx were not
correlated with the evidence of myocardial involvement in previously reported
cases. This may be of extreme importance in an attempt to evaluate the imme-
diate significance of the electrocardiographic changes as well as the future outlook
for the patient in view of the opinion recently expressed by Rantz, Boisvert, and
Spink.^®

These authors obtained electrocardiographic evidence of carditis similar
to that described here in 10.8 per cent (twenty cases) of 185 patients on whom
serial electrocardiograms were taken during and following Group A beta hemo-
lytic streptococcal throat infections. A true latent period between recovery
from the sore throat and the development of changes in the electrocardiogram
occurred in only six of these patients. When a latent period was demonstrated,
reinfection by a new type of Group A streptococcus had frequently taken place.

Because carditis was not demonstrable in 80 per cent of their series, a toxic
etiology for the carditis in the group with no latent period was rejected. Pre-

young: ECG changes and upper TIESPIRATORY infections 391

viously unrecognized streptococcic respiratory infection with the establishment
of an abnormal tissue sensitivity was postulated as the mechanism for the patho-
genesis of the myocardial involvement in these patients. In those patients in
whom a latent period between the respiratory infection and carditis occurred,
the same mechanism was considered responsible because a new type of Group A
streptococcus was discovered in the throat on subsequent cultures. Thus these
authors suggested grouping cases of carditis with and without a latent period
following the acute respiratory phase, rheumatic fever, and postscarlatinal arth-
ritis under the term "poststreptococcic state.”

If one is inclined to accept this attractive hypothesis, then the electro-
cardiographic changes demonstrated at least in some of the thirteen patients in
the present study assume an even greater potential significance. Five of these
patients repeatedly showed a Group A hemolytic streptococcus in the naso-
pharynx during the acute phase and during convalescence. Of these five, two
patients had definite infectious mononucleosis. Although a study previously
carried out at this hospital demonstrated a Group A carrier rate of only 1.9
per cent in this geographic area^^ it is quite possible that the organisms were not
responsible for the disease process in the two patients with infectious mono-
nucleosis and that they Avere merely carriers of the hemolytic streptococcus. A
Group B hemolytic streptococcus was isolated in one case. This organism is not
infrequently found in the upper respiratory tract and is usually not pathogenic
for man. In one case a Group G streptococcus was repeatedly isolated. This
type may at times be of clinical significance.

Granting that five and possibly seven cases were actually infected with
hemolytic streptococci, it is to be noted that comparable electrocardiographic
changes occurred in six patients from whose throats at no time unusual organisms
were isolated. This certainly suggests a nonspecific to.xic process as the causa-
tive mechanism and can just as readily be applied to those cases in which path-
ogenic organisms were demonstrated as can the theory of specific sensitization
of the myocardium by products of the hemolytic streptococcus.

In regard to the “streptococcal group” of cases, and perhaps even in the
others, the mechanism of the production of carditis is of more than academic
importance. Neither the study by Rantz, Boisvert, and Spink*" nor this study
reveals the eventual outcome in such patients. It is well known that signs of
valvular disease may not appear for a considerable period of time after all evi-
dence of rheumatic fever has subsided. Many studies have also shown that in
from 25 to 50 per cent of patients in whom rheumatic heart disease is found, no
antecedent history of rheumatic fever can be obtained. Thus, if such patients
who demonstrate evidence of carditis during respiratory infection without other
accepted criteria of rheumatic fever*- are considered to be in the same group as
those with the “rheumatic state,” then prognosis in such patients must be guarded,
and certainly every effort must be made to prevent recurrent respiratory infec-
tion in such individuals. If, on the other hand, the underlying mechanism
is considered to be of nonspecific “toxic” origin and not related to a “rheumatic”
sensitization of cardiac tissue, then the possibility of progressive or future cardiac

392

AMERICAN HEART JOURNAI.

damage is considerably reduced and electrocardiographic changes assume much
less importance.

Upper respiratory infection has been at times cited as the cause of Fiedler’s
or diffuse isolated myocarditis. ^ Hansmann and Schenken'^ suggest that the
microscopic appearance of the muscle fibers in isolated myocarditis makes one
suspect that the same thing occurs in the milder forms of toxic myocarditis from
which patients usually recover without clinical recognition. Thus transient
electrocardiographic changes occurring in upper respiratory infections would be
considered to represent a. forme fruste of acute diffuse myocarditis.

Candel and Wheelock'* suggest this same possibility in discussing acute myo-
carditis following tonsillitis. They also speak of permanent abnormal electro-
cardiographic alteration. However, it would seem that in vietv of changes in
four of our cases persisting for forty-one, eighty-three, seventy-four, and seventy-
two d.ij’s, respectively, before returning to normal, it is dangerous to conclude
without a long follow-up period that permanent changes have resulted.

While it is most likely that the electrocardiographic changes in those patients
who received sulfadiazine in an attempt to eliminate the hemolytic streptococcus
from the nasopharynx were due to the respiratory infection, in view of recent
necropsy and experimental evidence of myocardial involvement due to sulfona-
mide ad ministration, this drug cannot be entirely excluded as an etiologic
factor. Electrocardiographic evidence of myocardial involvement due to sul-
fonamides alone has recently been obtained on six patients. This study will form
the basis of a subsequent report. In this particular series, however,, the drug may
at best be considered an additive toxic factor rather than the sole responsible one
for the electrocardiographic changes.

It is important' to note that in none of these thirteen patients did cardiac
signs or symptoms develop during the period when the electrocardiogram in-
dicated myocardial involvement. This is in marked contrast with the e.xperience
of Scherf,® who described weakness, palpitation, slight dyspnea, precordial or
substernal pain, apprehension, tachycardia, and, in more severe cases, cardiac
enlargement, gallop rhythm, and rarely congestive failure as occurring from one
to two da 5 '^s after the onset of acute tonsillitis or shortly after the acute respira-
tory phase had subsided. The discrepancy between these two reports may
possibly be attributed to the fact that our patients were all previously healthy
individuals with greater cardiac reserve. It is apparent that on the basis of the
clinical manifestations of the thirteen patients in this study, myocardial involve-
ment would not have been suspected, so that the present report can offer no in-
dications as to when or in which particular patients with upper respiratory^ in-
fection serial electrocardiographic studies should be made.

SUMMARY AND CONCLUSIONS

1. Thirteen cases of upper respiratory infection in which electrocardio-
graphic evidence of myocardial involvement was obtained are presented. Group

A beta hemolytic streptococci were isolated on throat culture from onlv five of
these thirteen patients.

393

young: ecg changes and upper respiratory infections .

2. The demonstration of comparable electrocardiographic changes in
patients with and without hemolytic streptococcal respiratory infection favors
a nonspecific toxic etiology as the underlying mechanism for both rather than the
theory of streptoccocal “rheumatic” sensitization of the myocardium.

3. Whether or not such cases represent a forme fruste of Fiedler’s myo-
carditis can only be speculated upon, but this possibility is worthy of serious con-
sideration.

4. The possible relation of sulfonamide administration to the development
of myocardial changes in some of the patients is mentioned, but this may be at
most an additive factor,

5. The absence of cardiovascular signs and symptoms in these patients is
noted, so that no clinical indications for electrocardiographic study in patients
with upper respiratory infection exist.

6. Present knowledge does not allow the inference that electrocardiograms
should be taken routinely during upper respiratory infection.

references

1. Saphir, O.: Myocarditis. A General Review With an Analysis of 240 Cases, Arch. Path.
32; 1000, 1941; 33; 88, 1942,

2. Finland, M., Parker, F., Jr., Barnes, M, W., and Jolliffe, L. S,; .4icute Myocarditis in In-
fluenza A Infections. Two Cases of Non-Bacterial Myocarditis With Isolation of Virus
From the Lungs, Am. J. M. Sc. 209; 455, 1945.

3. Candel, S,, and Wheelock, M. C.; Acute Non-Specific Myocarditis, Ann. Int. Med. 23;
309, 1945.

4. Editorial: Acute Non-Specific Myocarditis, J. A. M. A. 129: 1018, 1945.

5. Schultz: Quoted Saphir.^

6. Scherf, D.: Myocarditis Following Acute Tonsillitis, Bull. New York M. Coll. 3: 252, 1940,

7. Carr, J. G., and Walsh, J. A,: Acute Infectious Myocarditis, Illinois M. J. 65: 134, 1934.

8. Maher, C. C., and Wosika, P. H.: Electrocardiography, ed. 3, Baltimore, 1940, Williams &
Wilkins Co., p, 297.

9. Scherf, D., and Boyd, L, J.: Cardiovascular Diseases, St. Louis, 1939, The C. V. Mosby

Co., pp. 176-180. '

10. Rantz, L. A., Boisvert, P. J., and Spink, W. W.: Etiology and Pathogenesis of Rheumatic
Fever, Arch. Int. Med, 76; 131, 1945.

11. Glazer, A. M., and Gots, J. S.: The Incidence and Epidemiological Significance of Hemo-
lytic Streptococci in a Flprida Army Camp, South. M. J. 37 : 628, 1944.

12. Jones, T. D.: The Diagnosis of Rheumatic Fever, J. A. M. A. 126; 481, 1944.

13., Hansmann, G. H., and Schenken, J. R.: Acute Isolated Myocarditis; Report of a Case
With a Study of the Development of the Lesion, Am. Heart J. 15; 749, 1938.

14. Nelson, A. A.: Histopathological Changes in Hens and Rabbits Following Administration
of Sulfanilamide and Sulfanilyl Sulfanilamide (di-sulfanilamide). Pub. Health Rep. 54:
106, 1939.

15. French, A. J., and Weller, C. V.: Interstitial Myocarditis Following the Clinical and Ex-
perimental Use of Sulfonamide Drugs, Am. J. Path. 18; 109, 1942.

16. Lederer, M., and Rosenblatt, P.: Death During Sulfathiazole Therapy: Pathology and
Clinical Observations on Four Cases With Autopsy, J. A. M. A. 119; 8, 1942.

17. (a) Rich, A. R.: The Role of Hypersensitivity in Periarteritis Nodosa as Indicated by

Seven Cases Developing During Serum Sickness and Sulfonamide Therapy, Bull.
Johns Hopkins Hosp. 71; 123, 1942.

(b) Rich, A. R.: Additional Evidence of the Role of Hypersensitivity in the Etiology of
Periarteritis Nodosa, Bull. Johns Hopkins Hosp. 71; 375, 1942.

18. Simon, M. A., and Kaufmann, M.: Death Following Sulfathiazole Therapv, Canad. M. A.
J.48; 23, 1943.

19. ’ Rich, A. R., and Gregor}-, J. E.: Experimental Demonstration That Periarteritis Nodosa

Is a Manifestation of Hypersensitivity, Bull. Johns Hopkins Hosp. 72: 65, 1943.

20. Duff, G. L.: Quoted in Simon, M. A.: Pathologic Lesions Following the .Administration
of Sulfonamide Drugs, Am. J. AI. Sc. 205; 439, 1943.

21. Longseope, W. T.: Serum Sickness and Analagous Reactions From Certain Drugs Par-
ticularly the Sulfonamides, ATedicine 22; 351, 1943.

22. Black-SchaiTer, B.: Patholog}- of Anaphylaxis Due to Sulfonamide Drugs, Arch. Path.
39; 301, 1945.

Clinical Reports

COR BILOCULARE

Case Report

J. K. Bembenista, M.D.

Buffalo, N. Y.

C OR BILOCULARE is a rare congenital cardiac anomaly and was first
recorded by Wilson in 1798. Abbott, in a comprehensive study of con-
genital heart lesions published in 1936, recorded only fourteen examples of this
anomaly. Since then, five additional cases have been reported, two of which
occurred in twins.

Most subjects with this condition die in early infancy, although one patient
lived to the age of 18 years. The sex distribution is about equal. There are no
characteristic physical signs; no cardiac murmurs. or thrills have been described.
Cyanosis is the most prominent finding. Other anomalies may be associated
with this condition, the commonest of which is a persistent truncus arteriosus.

CASE REPORT

On March 12, 1941, a white baby girl, weighing 8 pounds and 11 ounces, was born at the
Mercy Hospital. The delivery was spontaneous from a vertc.x presentation under vinethene
anesthesia.

The mother was 36 years of age and has five other normal children. Her past history is not
remarkable. The child's father is living and well.

Immediately after delivery the child's color was good and it had a strong cry. About three
hours later, it was observed that the baby became cyanotic when she cried. Examination of the
infant at this time rev'ealed no other abnormalities. No murmurs were heard over the pre-
cordium. An x-ray film showed no enlargement of the thymus gland.

For the first few days of life the baby's color was fair until it sneezed or cried; then cyanosis
became pronounced. Later cyanosis became constant and was not relieved even when oxygen
was given continuously. The baby had several vomiting spells with emesis of blood-streaked
mucus. Its condition became progressively worse, and it expired the seventh day after birth.

Autopsy Findings . — External e.xamination showed a well-developed and fairly well-nourished
but cyanotic female infant; the only abnormality was a small angioma of the skin of the back.
Examination of the internal organs revealed no important findings except in the heart.

When viewed in situ, the portion of the heart usually formed by the right auricle was seen to
be slightly enlarged; the part of the left border of the heart usually formed by the left ventricle
appeared more globular than usual. The pulmonary artery was in its proper position. The
ductus arteriosus was present but somewhat narrow, especially in its mid-portion.

Received for publication October 13 , 1045 .

394

bembenista: cor biloculare

395

On opening the heart only one'atrial chamber was found, from which two auricular appendages
projected and into which all the veins entered. The common atrium communicated through a
large aperture with a thick-walled ventricle, which in turn emptied into a normal-sized, aorta.
Near the upper margin of the ventricle and in its anterior wall lay a small, fiat, slitlike cavity which
evidently was a rudimentary right ventricle. It communicated with the pulmonary artery
by an opening guarded by three small but normal valve cusps. Although this chamber com-
municated with the large ventricle by a tiny orifice, it contained no blood and apparently did not
function. This infant’s heart thus had only one atrium, one useful ventricle, one rudimentary
and nonfunctioning ventricle, and a small ductus arteriosus Blood entered the pulmonary artery
only through this insufficient ductus arteriosus.

On more detailed examination it was found that four large veins entered the atrium. Oh
the right side superiorly was the opening of the superior vena cava. The posterior margin of this
opening was formed by a small muscular bundle, forming a semilunar ridge. This normally is
the upper limbus of the foramen ovale. Posterior to and iust below the orifice of the superior
vena cava, the right and left pulmonary veins entered. Below these lay the opening of the in-
ferior vena cava. This opening was partly covered by a fibromuscular membrane which most
likely was .the rudiment of the interatrial septum. The opening of the coronary sulcus lay be-
tween that of the inferior vena cava and the atrioventricular aperture.

Fig. 1. — The single auricle and the only functioning ventricle are shovai.

The atrioventricular opening was 4 cm. in circumference and was guarded by four unequal
valve leaflets, to which were attached four groups of papillary muscles.

The ventricle was as large as the combined right and left ventricies of a normal heart at birth.
The thickness of its muscle wall averaged 6 millimeters. From its superior portion arose the
aorta with a normal semilunar valve composed of three cusps. Just below the base of the right
posterior cusp of this valve was a tiny opening in the wall of the ventricle. This tiny orifice was
the only communication between the large ventricle and the slitiike cavity of the rudimentary-
right ventricle previously described.

The pulmonary artery was in its normal position and was guariled by three small cusps of
the pulmonarv valve The coronary arteries were not remarkable.

'I'he lungs, liver, spleen, and kidneys showed passive congestion.

396

AMERICAN HEART JOURNAL

SUMMARY

The heart described was unusual in that it consisted primarily of only one
atrium and one ventricle with a patent ductus arteriosus. The ventricle had a
rudimentary slitlike cavity in its wall, but this to all intents and purposes was
nonfunctioning.

This case, we feel, is a cor biloculare.

REFERENCES

1. Tow, A.; Cor Biloculare With Truncus Arteriosus and Endocarditis, Am. J. Dis. Child.
42: 1413, 1931.

2. Abbott, M. E.: Atlas of Congenital Cardiac Disease, New York, 1936, The American
Heart Association.

3. Davies, F., and AlacConaill, M. A.: Cor Biloculare W'th Note on Development of Pul-
monarj' Veins, J. Anat. 71: 437, 1937.

4. Guistra, F. X., and Tosti, V. G.: True Cor Biloculare in Identical Twins, Am. He.art J.
17: 249, 1939.

5. Beniamin, J. E., Landt, H., and Zeek, P.; Persistent Ostium Arterioventriculare Commune
in Heart Which Functioned as Biloculate Organ; Report of Case, Including Autopsy', in an
Eighteen-Year-Old Girl, Am. Heart J. 19; 606, 1940.

6. Rossman, J. I.; Cor Biloculare With Transposition of Great Cardiac Vessels and Atresia
of Pulmonary Artery, Am. J. Clin. Path. 12: 534, 1942.

7. Michelson, R. P.; Cor Biloculare With Persistent Truncus Arteriosus, Am. Heart T- 25:
112, 1943.

Letters

To THE Editor:

In a paper in the April, 1946, issue of the American Heart Journal (voI. 31, pp. 473 to
476) on the duration of the P-R interval and its relationship to the cycle length, the author states:
“It is seen that although there appears to be a tendency for the P-R interval after exercise to
be shorter, the difference is more apparent than real. For the P-R values after exercise to be sig-
nificantly different from those found before exercise, a difference greater than three times the
standard deviation should be present. In this series the difference was less than even twice the
standard deviation.” Table II (p. 476) shows in a large number of young men a mean P-R
interval of 0.143 sec. and a standard deviation of 0.014 sec. before exercise, and of 0.129 and of
0.010 sec., respectively, after exercise. It is not clear whether the author refers in the section
quoted to mean P-R values or to the P-R interval in the individual case. His own data (Fig. 1,
p. 474) show definitely that the mean P-R interval is shorter at short than at long cycle lengths.
This is demonstrated by the following facts: The mean P-R interval of the 189 individuals
(Fig. 1) whose cycle lengths were below 0.46 sec. is 0.123 + 0.00C68 sec., and the standard devia-
tion is 0.014 ± 0.00C47 sec. The 160 individuals whose cycle lengths exceed 0.79 sec. have a mean
P-R interval of 0.1475 + 0.00091 sec. and a standard deviation of 0.017 + 0.0DC64sec. The differ-
ence between the means is 0.0247 ± 0.00114 sec., or over twenty times its probable error. (See
Raymond Pearl, Introduction to Medical Biometry and Statistics, Philadelphia, 1930, W. B. Saund-
ers Co,, p. 283, et. seq.) Hence it is clear that the mean P-R interval shortens as the heart rate
increases, and there is no doubt, in view of the large number of persons studied, that the figures
given by the author in his Table II prove this just as conclusively as the above analysis. In con-
trast to these statements about the mean interval, in the single case among healthy male adults
in the age range studied, the P-R being measured by the author’s technique, the odds against the
interval falling outside the range set by three standard deviations is about 370 to one.

In an earlier paper (.‘\m. Heart J. 31: 329, 1946) the same author states that the relationship
between the Q-T interval and the cycle length is linear. In this case it is also possible to demon-
strate from the data given on p. 330 that the relationship in question is actually curvilinear (Pearl:
p. 386 et seq.), and this evidence becomes overwhelming when the data supplied by other authors
are also treated statistically.

Richard .Ashman

Louisiana State School of Medicine, New Orle.a.ns.

The following is a reply to Dr. .Ashman's letter:

To the Editor:

In the section of the paper quoted (vol. 31, p. 473) and Table II (p. 476), the mean P-R
values referred to are the means of all the individual P-R measurements. This was broken down
into (a) the mean value of all the P-R intervals before exercise, and (b) the mean value of all the
P-R interv'als after exercise. Thus, a comparison was made between the P-R intervals
of the same individual or group at different heart rates. However, no such comparison
between individuals was made or implied by this treatment of the data. This treatment
was used to indicate what the chances were for a healthy male individual chosen according to the
criteria outlined in the article to show differences between P-R intervals at different heart rates
greater than three standard deviations. As Dr. Ashman points out, the odds arc approximately
370 to one against such an occurrence.

397

398

AMERICAN HEART JOURNAL

The bccond point made by Dr. Ashman, that the mean P-R interval shortens as the cycle
length shortens, does not contradict any statement in the article. Not only does Fig. 1 (p. 474)
show this to be true, but the coefficient of correlation that was calculated and found to be plus
0.387 shows this even more clearly. Yet, what docs this mean? Showing that the P-R interval
is shorter at shorter cycle lengths is only a qualitative analj’sis. When this is studied quanti-
tativel}' b}’ determining the coefficient of correlation it is found that, although there was such a
relationship between P-R and C, the low order of magnitude of this coefficient indicates that this
relationship is not of importance.

In studying the relationship of QT to cycle length (vol. 31, p. 329), Fisher’s method of analysis
of variance was used to determine whether or not the actual data deviated significantly from
linearity. It was found that the deviation was not significant. This method was used because
it was recognized as one that would give an accurate analysis of the data. Dr. Ashman
applied another method of analysis to the same data. I agree with Dr. Ashman that,
when this other method, the Correlation Ratio (eta) and Blakcman’s Criterion, is used, there
appears to be significant deviation from linearity. The question that arises is why should the
same data, when analyzed by two methods, yield different interpretations. Apparently, the
difference arises from the methods used. The Correlation Ratio and Blakeman’s Criterion do
not take into account the number of assays. A more detailed discussion of this can be found
in Fisher, R. A.; Statistical Methods for Research Workers, ed. 6, p. 263. Because of the limi-
tations inherent in the latter method, Fisher’s method of analysis of variance was felt to be the
more desirable and more accurate.

There is one point I wish to make. In analyzing the data it was realized that our data formed
a regression within certain limits. Thus, we were studying only one segment of a curve or line
that theoretically may extend much beyond the limits set by our study. Let us assume for argu-
ment’s sake that this segment is part of a curt'c or even a circle. Tliis circle may have a radius
of such magnitude that the regression set by our limits forms a relatively small segment of this
circle. It is known that as the ratio of segment to radius becomes smaller and approaches zero,
the segment approaches a straight line. Thus, the QT/C regression studied here may be a small
segment of a much greater curve, and analysis of this segment per se may fail to reveal significant
deviation from linearitj- when only 1 ,400 measurements arc used. However, if 14 million measure-
ments were analyzed we might then find that the deviation from linearity which was not significant
when 1,400 were studied is now significant.

Thus, although this study failed to reveal significant deviation from linearity, it is under-
stood that the regression might still be curvilinear. For practical purposes, however, treating
this data as a linear regression is adequate.

Isidore Schlamowitz. M.D.

Abstracts and Reviews

Selected Abstracts

Henry, G. C., and Boone, A. A. : Eleclrokymograph for Recording Heart Motion Utiliz-
ing the Rocntgenoscope. Am. J. Roentgenol. .'54: 217 (Sept.), 1945.

Although graphic recording of the motion of the heart and great vessels has been a long-
desired goal, this method has not been used extensively because of analytic difficulties in the size,
clarity, and brevity of the recorded waves to be examined on the kymogram and the time-con-
suming nature of the anaij'sis. The authors have developed a method which overcomes these
difficulties and produces a large, beam type or electrocardiographic type of tracing on bromide
paper of a chosen point of the cardiac silhouette.

Under the rocntgenoscope, the diaphragm of the electrokymograph, which contains a narrow
slit, is aligned at right angles to the particular portion of the heart border to be investigated.
As the heart beats, its border moves back and forth across the slit, varying the intensity of the
roentgen rays passing through it. If the intensity of these rays were recorded with distortion
in respect to a time axis we would have an indication of the motion of this portion of the heart
border. This is accomplished by a 931-A multiplier phototube, used by Morgan in his exposure
meter for roentgenography. A strip of fluoroscent screen is placed directly over the photosensi-
tive area of the 931-A tube. As roentgen rays strike the tube, the cathode is illuminated. When
the shadow of the heart border moves inward (contractile motion) this strip of screen is further
irradiated by the beam. Thus, the total light emitted is proportional to the changes in the position
of the heart border. The current output is amplified and recorded by a galvanometer. Tracings
of the carotid pulse are recorded simultaneous^' to align curves from separate points on the
cardiac border in respect to the time relations in the cardiac cycle.

Sample records are presented which represent the motion of the left ventricular border,
the pulmonary artery, the aortic knob, and the right auricular border. These are aligned, one
above the other, by the carotid pulse tracing, so that events or different records falling on anj'
given vertical line occur at the same time. The wave forms for each of the border areas of the
heart are found to be characteristic of that particular area and they resemble closely the respective
volumetric wave forms found in physiology texts.

These authors expect to present more detailed Information regarding the individual chambers
of the heart in subsequent papers, Serber.

Dobson, C.: Subacute Bacterial Endoearditis Complicated by Pregnancy, Successfully
Treated With Penicillin. Am. J. Obst. & Gynec. 51: 427 (March), 1946.

The patient, a 24-year-old gravida ii, para O, entered the hospital Jan. 2, 1945, for a thera-
peutic abortion. She gave a history of having had a cold for the preceding two weeks, complicated
by backache, low-grade fever, nausea, and occasional tenderness in several of the digits. She
presented evidence of rheumatic mitral and aortic disease, and two blood cultures were positive
for Streptococcus viridans. Penicillin administration was begun on Jan. 14, 1945; 200,000 Oxford
units were given daily in divided doses. On Januar>' 13, the blood culture was negative. Re-
peated subsequent cultures were negative. .After five weeks of penicillin therapy her progress
was not satisfactory', and it was considered advisable to interrupt the pregnancy, which was

399

400

AMERICAN HEART JOURNAL

terminated on the nineteentli of February. The patient was discharged on March 18, 1945,
nine da 3 's after penicillin was discontinued. The cardiac re.serve was good, and the patient was
considered to have recovered from subacute b.acterial endocarditis. Bei,u:t.

Hunter, W. S.t Coronary Occlusion in Negroes. J. /\. M. A. 131: 12 (May 4), 1946.

This author, after reviewing the literature and as a result of his own observations and ex-
periences, concludes that the diagnosis of coronarj' occlusion is rarely made ante mortem in
Negroes. He gives as reason for this the fact that, during the episode of coronary occlusion,
dyspnea is the chief complaint and pain is absent. Me reviewed a serie.s of 1,000 consecutive
autopsies on Negroes and 1,000 consecutive autopsies on white patients at the Louisville General
Hospital over a ten- j'car period. He found that below the age of 70 j’cars the incidence of myo-
cardial infarction was approximately the same in both Negro and white patients. Dvspnea rather
than substernal pain was the outstanding presenting symptom in all the Negroes prior to death.

Hunter stresses the point that careful clinical and electrocardiographic examination of
Negroes with acute left ventricular failure will reveal many diagnose.s of coronar>' occlusion.

Beulet.

Weinrolli, L, A., and Ilerzstcin, .1.: Relation of Tobncco Smoking to .Artcrio.sclerosis

Obliterans in Diabetes Mellitus. J. A. M. 131: 205 (May 18), 1946.

The purpose of this study was to determine the relative incidence of occlusive arterial disease
in diabetic patients who smoked, as compared with a similar group who abstained from the use of
tobacco. The findings indicate the significantly higher incidence of occlusive vascular disea.se
in diabetic patients who vised tobacco as compared with diabetic nonsmokers. This held true
in all decades up to 70 years. The reason for the increased frequency of occlusive arterial disease
which they have observed in diabetic smokers is not clear The authors suggest that over a period
of time by virtue of its vasoconstrictor effect, tobacco may cause an already constricted arteri-
osclerotic vessel to become still further narrowed. Such encroachment on the lumen would favor
thrombus formation. A lowered frequency of arteriosclerosis obliterans prevailed in general
among nonsmokers regardless of such factors as severity of the illness, adequacy of control, and
the presence of obesity or hypertension. Bellet.

Bauer, G.; Heparin Therapy in Acute Venous Thrombosis. J. .A. M..'\. 131: 196 (Ma\' 18).

1946.

This author difiterentiates between the inception and course of occlusive disease of the super-
ficial and deep veins. In superficial veins, thrombophlebitis is the primary disorder and is followed
secondarily by thrombotic obliteration of the venous segment involved. In the large deep veins
of the legs the process begins with a thrombus which arises in a muscle vein and projects into the
lumen of one of the large venous trunks of the lower part of the log. Here it becomes the starting
point for the deposition of a thrombus which extends upward and, in about 80 per cent of the
cases, reaches the femoral vein. This process, which generallj’ lasts about twentj’-four to forty-
eight hours, may result either in the formation of an embolus, or, by far the most common course,
the thrombus may grow in thickness and block the lumen of the femoral vein along its entire
length and produce t\’pical phlegmasia alba dolens. Complications of this process in the chronic
stage are permanent swelling of the legs, indurative lesions, and leg ulcers in a large percentage of
cases. The author emphasizes the importance of early diagnosis of this condition which is sug-
gested bj' the presence of tenderness in the back of the calf accompanied by mild swelling and pain
in this region. The diagnosis is confirmed by phlebography which presents a rather charac-
teristic picture. The opinion is given that phlebography should constitute a routine method of
study in all cases of suspected early thrombosis. Remarkable improvement followed the earl\’
institution of heparin therapy. In addition, forceful active leg movements were instituted im-
mediately after the diagnosis was established. The mortality from thromboembolism under this

SELECTED ABSTRACTS

401

treatment was decreased to less than one-tenth of what it formerly had been. The length of stay,
in bed was reduced from forty days to less than five days, and incapacitating aftereffects did not
appear in the majority of cases so treated. Bellet.

Manchester, R. C.: Rheumatic Fever in Naval Enlisted Personnel. III. The Physio-
logic and Toxic Effects of Intensive Salicylate Therapy in Acute Cases, J. A. M. A.
131: 200 (May 18), 1946.

Following the regimen outlined by Coburn, thirty-five patients with acute rheumatic fever
received daily intravenous doses of 10 Gm. of sodium salicylate dissolved in 1 liter of saline solu-
tion or Ringer’s lactate solution for four to ten days. Nineteen additional patients received oral
therapy throughout the course of treatment, which consisted of between 10 and 12 Gm. of acetyl-
salicylic acid or sodium salicylate daih', usually in conjunction with 8 Gm.of sodium bicarbonate.
Under this regimen, toxic reactions of serious proportions occurred, but these were preventable in
most instances. Hypoprothrombinemia occurred frequently, reaching a maximum in the first
week of salicylate administration, but improved spontaneously thereafter even though large
doses were continued. No instance of hemorrhage as a result of hypoprothrombinemia was
observed. The alkali reserve was depleted unless adequate amounts of alkali were given in con-
junction with salicylates. When large doses of salicylates were given orally, between 0.8 and I
Gm. of sodium bicarbonate was given with each gram of salicylate. For the same reason, intra-
venous salicylates should be administered in Ringer’s lactate solution instead of saline solution.

Severe delirium, “acute saiicylism,’’ is dependent on the rapid rise in blood salicylate levels
associated with intravenous therapy and occurs most often in acutely ill patients who have not
built up an antecedent tolerance to the drug. It was not observed in this series, following oral
therapy.

The author found that serum salicylate levels of 25 mg, per 100 c.c. or higher have been
found to suppress rheumatic infection satisfactorily. Salicylate therapy was continued until the
erythrocyte sedimentation rate had been normal for two weeks. Bellet.

Bourne, G.: Bicuspid Aortic Valve Diagnosed During Life. Brit. M. J. 1: 609 (April 20),

1946.

This author discusses criteria upon which he believes a diagnosis of bicuspid aortic valve
may be made during life. These are the appearance of the signs and symptoms of subacute bac-
terial endocarditis and accompanying aortic insufficiency in an individual, usually young, who
has previously been carefully examined and in whom there was no evidence of heart disease of
any kind. Since bacterial endocarditis rarely develops upon a normal aortic valve, the sudden
appearance of aortic regurgitation together with infective symptoms in a previously normal
person is extremely suggestive of the presence of a bicuspid valve. The diagnosis was made in
life and confirmed by necropsy in a case presented by the author. Bellet.

Lenegre, J., and Maurice, P. : Some Results of Recording Electrical Currents From the

Right Auricle and Ventricle by the Direct Intracavity Lead. Arch. d. mal. du coeur.

38:298 (Nov.-Dee.), 1945.

The authors report some of their results in electrocardiograms recorded from within the right
auricle and ventricle in man. Their technique involved the use of a soft exploring electrode of
tin which projects from the end of a No. 13 ureteral catheter. A gold wire in the lumen of the
catheter connected the lead wire to the electrode. The catheter was inserted into an antecubital
vein and, under' fluoroscopic obserx^ation, was passed into the right auricle or ventricle. The
indifferent electrode was placed on the left leg. The intra-auricular and intraventricular leads
were recorded simultaneously with the three limb leads.

Records obtained from within the right auricle showed rapid auricular waves of considerable
amplitude which were often analogous to those obtained from an esophageal lead. Records ob-

402

AMERICAN HEART JOURNAL

tained from within the right ventricle indicated clearly the sequence of ventricular activation in
extrasystoles and in bundle branch block. Current views on the interpretation of electrocardio-
grams in these conditions were confirmed.

It is emphasized that electrocardiograms .from the intracavity leads must be interpreted
with some caution because of artefacts which are inherent in the technique. There is no certainty
as to which part of the cavity wall is in contact with the electrode nor is there any assurance
that the contact is constant because of the movements of the heart. Some of the resultant arte-
facts are obvious, but others may be less apparent. The procedure is considered valuable, how-
ever, for the study of arrhythmias and conduction defects. L.vpl.vce.

PrUche, A: Cardiodynamometry. A Practical Test for Determination of the Func-
tional Capacity of the Heart. Arch. d. mal. du coeur. 38:264 (Nov.-Dee.), 1945.

The author states that the criterion for the functional capacity of the left heart is the supply
of an adequate amount of blood to the peripheral tissues in proportion to their activity, while
that of the right heart is the withdrawal of an adequate amount of blood from the venous system
to prevent peripheral congestion. As a test of cardiac function based on this concept, he uses the
following procedure. The patient is placed in a recumbent posture with one arm held at a right
angle to the body. An armlet connected to a water manometer is placed on the upper arm.
A second armlet connected to a plethysmograph is placed on the lower hrm. The subject rises,
performs a standard exercise of twenty deep flexions of the legs, and lies down. Measurements
of the circulation are made immediately. The subject then rises, makes fifty deep flexions, and
again lies down, whereupon the measurements are repeated.

Three determinations are made. The first concerns the pressure in the return circulation
(PV). The pressure in the upper armlet is gradually increased and a notation is made of the
level at which beginning congestion in the lower arm is indicated by the plethysmograph. This
is considered to be the venous pressure in the arm. The second determination concerns the systolic
index (IS). At the moment of recording PV, the upper armlet pressure is rapidly increased to
80 cm. of water and the resulting upward deflection of the plethysmographic indicator for a period
of exactly ten seconds is recorded. The third determination concerns the volumetric index (V).
This is the relation of IS to the number of pulses noted during ten seconds from the moment of
establishing the IS. It represents the volume of blood entering the distal segment of the limb.

Criteria for a normal cardiodynamic status are: For PV, constant or little variation through-
out the test; for IS, in relation to its control valve, IS increases two points for the first e.xercise
and four points for the second; for V, no significant change.

Results of the application of this test to ambulatory cardiac patients are reported. It is
emphasized that a normal test does not necessarily indicate absence of organic heart disease, nor
does an abnormal result indicate the existence of organic heart disease. The test affords simply a
quantitative estimate of the functional capacity of the heart. Laplace.

Penner, S. L., and Peters, M.: Longodty With Ventricular Aneurysm; Report of a
Case With a Survival Period of Fifteen Years. New England J. Med. 234:523 (April
18), 1946.

The case is reported of a 43-year-old infantry officer who had a severe anginal attack in Octo-
ber, 1929. A second attack, accompanied by shock and an audible friction rub occurred in Novem-
ber, 1929. A third attack, also accompanied bv an audible friction nib, occurred in January,
1930. The electrocardiogram showed evidence of a typical acute anterior infarction. Recovery
ensued without congestive failure but the patient remained in the hospital for one year. There-
after he led an active life and in September, 1942, he returned to the Army on limited duty.
In September, 1944, he had a recurrence of moderate anginal pain and dj'spnea on effort. X-ray
examination showed slight cardiac enlargement and, overlying the left ventricular portion of the
cardiac silhouette, a thin curvilinear band of calcification forming the outer half of a soft tissue con-
densation. Fluoroscopy revealed that the calcification was in the outer surface of an outpouching

SELECTED ABSTRACTS

403

of the anterior surface of the left ventricle. No pulsation in the area was noted. A diagnosis of
left ventricular aneurj-sm with calcification of the ventricular wall was made. The patient’.':
symptoms subsided and when last seen on Sept. 6, 1945, he was feeling well and enjoying deep-sea
fishing. , ,

It is pointed out that the aneurysm in this case had probably been present for fifteen years.
The fact that the patient remained in the hospital for an entire year follo\\ing his initial illness is
considered responsible for the unusual degree of recover 5 c Laplace.

Stearns, S., Riseman, .J. E. F., and Gray, W.: Alcohol in the Treatment of Angina
Pectoris. New England J. Med. 234:578 (May 2), 1946.

Observations were made on the therapeutic effect of alcohol in a series of twenty-one patients
who had angina of effort. The series included nineteen men and two women. Their ages ranged
from 39 to 75 years. Only one had had recent cardiac infarction and none had congestive failure.
Control determinations were made of the patients’ ability to work by subjecting them to the
Standardized E.xercise Tolerance T^st which consists of continuously ascending and descending a
two-step staircase in a cold room. The effect of alcohol was then studied by repetition of the test.

Twenty-one patients took one ounce of whisk}' at various times up to ninety minutes before
the test. Five of the patients were able to perform from 18 to 27 per cent more work than was
otherwise possible. Nine patients drank one ounce of whisky four times daily for a week prior
to the test. Of these, two patients had no attacks of pain during the week but had no demonstrable
increase in exercise tolerance, while in two patients, the angina became worse’ during the week.
Five patients felt subjectively better; in one, exercise tolerance was increased 23 per cent and in
another, it was decreased 33 per cent.

When one-half ounce of whisky was held in the mouth during the test in order to demonstrate
a possible reflex effect, there was no change in pain or in exercise tolerance.

Tt is concluded that therapeutic doses of whisky do not measurably shorten the duration of
attacks or increase the work capacity of patients who have angina pectoris. Many patients are
■ afforded an increased sense of well-being but others are made worse.

Laplace,

Froment, R., Guinel, P,, Vignon, G., and Martin-Noel ; Atheromatous Coronar}' Dis-
ease of Early Onset and Parallel Course in Twins. Arch. d. mal. du coeur. 38:260
(Nov.-Dee.), 1945.

Two cases are reported of homologous twins who were apparently in excellent health until the
age of 34 years when, within a few weeks of each other, both began to have typical severe angina
of effort. ' Both had mild hypertension. Nine months later, the first twin died suddenly after
several days of recurrent .spontaneous anginal attacks. Autopsy showed almost complete ather- .
omatous obliteration of all the large coronary arteries together with diffuse myocardial degenera-
tive change.

In the case of the second twin, the angina of effort persisted for several months but by the
following year had disappeared completely. Three years later, angina reappeared in mild form
and then suddenly a severe spontaneous attack occurred, during which the patient died. No
autopsy was performed but an electrocardiogram taken two years previously had shown flat. T-

and a deeply negative pointed Tj.

These cases emphasize strongly the familial character of cononary artery disease.

L.aplace.

Froment, R., and Gonin, A.; .-Vorlic Stenosis Due to Calcified Syphilitic Valvulitis.
Arch. d. mal. du coeur. 38:257 (Nov.-Dee.), 1945.

Three cases are reported in which aortic insufficiency caused by syphilitic, valvulitis was
accompanied by a substantial degree of stenosis. Autopsy revealed that the cause of the stenosis

404

AMERICAN HEART JOURNAL

in all cases was secondary calcification which had involved a sufficient area of the affected valves
to prevent their complete opening.

It is pointed out that aortic stenosis of sufficient degree to be recognized clinically is generally
considered to be evidence against syphilis as the cause of the valve lesion. The three reported
cases are cited as exceptions to this rule. It remains true that syphilis does not produce aortic
stenosis but there are, nevertheless, rate instances of syphilitic aortic valvulitis in which a moderate
degree of stenosis may occur as a result of partial secondary calcification of the valve leaflets.

LAFLxVCE.

Lium, R.: Cardiac Arrest After Spinal Anesthesia. Report of a Case With Recovery.

New England J. Med. 234:691 (May 23), 1946.

The case is reported of a 62-year-old woman who was admitted to the hospital for a chol-
ecystectom}'. No preoperative cardiovascular abnormality was noted except a blood pressure of
180/90 ' The preoperative medication included pentobarbital sodium, 0.2 Gm., at bedtime,
which was repeated one hour before operation, and morphine sulphate, 10 mg., one-half hour before
operation. Spinal anesthesia was effected by pontocaine, 18 mg. in 3 c.c. of 10 per cent glucose,
placed in the subarachnoid space through the third lumbar interspace. Operation was begun
eleven minutes after the administration of the anesthetic. The patient stopped breathing forty-
three minutes later. A right rectus incision had been made and the heart could be palpated
through the diaphragm. No impulse was detectable. Cardiac massage was immediately in-
stituted by compressing the heart against the chest wall. With each compression the heart
flickered a little more firmly and a slow spontaneous beat was suddenly established five minutes
from the onset of cardiac arrest. Blood pressure immediately rose from 0 to 170/90. Periods
of artificial respiration had been alternated with those of cardiac massage. Spontaneous respira-
tion was resumed thirty-five minutes later and the operation was completed.

The patient’s general response for twenty-four hours after operation tras that of a decerebrate,
but complete recovery occurred during the ne.\t three days. The precise mechanism of this
type of anesthetic accident is undetermined. In most cases, cardiac massage and artificial res-
piration with pure oxygen are capable of reviving the heart. Lapl.\ce.

Bridges, W. C., Wheeler, E. O., and While, P. D.: Low-Sodium Diet and Free Fluid

Intake in the Treatment of Congestive Heart Failure. New England J. Med. 234:573

(May 2), 1946.

The treatment of cardiac edema by restricting sodium and permitting a free fluid intake has
not yet received wide application, although its usefulness is now generally appreciated. At
the Massachusetts General Hospital, sixty-four patients who had congestive heart failure were
treated by this technique as well as with digitalis, diuretics, and other routine measures.
Seventeen patients obtained much help, fifteen moderate benefit, eight slight benefit, and
seven no benefit. In the remaining seventeen cases, the patients were either uncooperative or
the data were insufficient to warrant inclusion in the present report.

The diet used contained about 700 mg. of sodium in an amount of food equivalent to 1,800
calories. If the food tasted too flat, ammonium chloride was used in place of salt. It was essential
that no salt or soda be used in cooking or included in incidental medicines.

The advantages of the treatment are that it frequently permits control of edema that cannot
be controlled otherwise, diminishes the frequency with which mercurial diuretics must be given,
and enables the patients to take more water. The disadvantages are the difficulty of preparing
or obtaining the diet outside of a hospital and the flat taste of the food.

The optimum amount of water to be taken has not yet been determined and it is uncertain
whether 5,000 to 6,000 c.c. per day is more beneficial than 2,000 to 3,000 c.c. Undoubtedly,

. however, the water intake formerly recommended was distinctly inadequate because diminished
renal function often prevents sufficient excretion of waste products when the daily fluid intake
is less than 1.500 c.c. Laplace.

SELECTED ABSTRACTS

405

Bachman, A. L.; Quantitative Roentgenagraphic Method for the Determination of

Left Auricular Size. Am. J. Roentgenol. 55:427 (April), 1946.

The importance of roentgenographic evidence of enlargement of the left auricle in the diagnosis
and management of rheumatic heart disease is at present generally accepted. The roentgeno-
graphic recognition of normal or markedly enlarged left auricles offers little difficulty. However,
considerable difficulty is encountered in the diagnosis of slight enlargement of the left auricle.
Much of this difficulty is due to the wide variation in the outline of the auricle in normal cases
and to the absence of a sharply defined difference between the appearance of the normal and
minimally enlarged auricular chamber.

The purpose of this paper is to demonstrate the amount of roentgenographic variation in the
appearance, of the left auricle in healthy individuals and to furnish quantitative standards estab-
lishing the distribution range for this normal variation. The anatomy of the esophagus and its
relation to the neighboring structures in the anteroposterior and the oblique rdews is discussed in
detail. At the site of the three main impressions, the aortic, the pulmonarj’-, and the left auricular,
the esophagus shows local posterior bulges but resumes its general downward and anterior direction
immediately below the indentations, A short distance (0.7 cm.) below the lower end of the aortic
indentation is the inconstant bronchial impression. The best indicator of the general esophageal
course is the direction of the “alpha” segment, which is located below the bronchial indentation,
since there are no local impressions by adjacent viscera on this portion of the esophagus. The
angle which the posterior border of the opacified e.sophageal “alpha” segment makes v.dfh the ver-
tical axis has been designated as “gamma” and is an index of the general esophageal course. The
angle between the downward extension of the posterior border of the “alpha” segment, and the
posterior margin of the esophagus in the upper portion of the auricular impression has been desig-
nated as the angle “theta.”

The left auricle, as it enlarges, expands in a posterior direction early in its course; upward
enlargement is usually seen shortly afterward. Posterior displacement is indicated in the early
phases by an increase in the angle between the lower end of the “alpha” segment and the upper
portion of the auricular impression (that is, the angle “theta”).

Methods were therefore employed to yield quantitative measurements for the indices of left
auricular size: (1) the angle “theta," (2) “M. P.,” which is the distance from the most posterior
point on the posterior border of the esophagus in the auricular region to a vertical line dropped
from the most posterior point on the border of the esophagus to the region of the aortic knob in-
dentation, and (3) the angle “gamma.” A series of other measurements, namely, (a) the height and
weight relationship, (b) frontal cardiac area, (c) transcardiac diameter, and (d) thoracic height,
were also made and statistical correlations calculated between these external somatic factors and
the three main indices.

. Two hundred fifty healthy male soldiers between 18 and 30 years of age were selected following
a physical examination in which rheumatic and other types of heart disease were ruled out.; A
set of four roentgenograms were obtained for each examinee, measurements as outlined were
made, and a series of normal standards created. The views employed were posteroanterior in
mid-inspiration, right anterior oblique in mid-inspiration, left lateral in mid-inspiration, and right
anterior oblique in mid-expiration.

The quantitative analysis method was found not only of great aid in establishing the diagnosis
of slight left auricular enlargement, but also was of considerable value in following patients where
the diagnosis was made in the initial examination. In the presence of conditions which grossly
alter the course of the esophagus, measurements were obviousl}’- invalid. These conditions in-
cluded aneurysm of the aorta, substernal goiter, arteriosclerosis with tortuosity, mediastinal
tumors, pulmonary fibrosis, and pericardial effusion. Bellet.

Gravelle, L. J., and O’Donnell, C. H.: Lumbar Sympathectomy for Chronic Leg
, Ulce’rs. Am. J. Surg. 71:620 (May), 1946.

Twent 3 '-one patients with chronic leg ulcers were treated by lumbar sympathectomy with
good results in twenty. The ulcers were due to venous stasis, arterial disease, and trauma.

406

AMERICAN HEART JOURNAL

A rise in skin temperature after lumbar paravertebral block was used as a criterion in selecting
patients for sympathectomy. Removal of the second and third lumbar ganglia proved satis-
factory for sympathetic denervation of the lower extremity. N.mde.

Farinas, I*. L ; Retrograde Abdominal Aortography. Am. J. Roentgenol. 55:448

(April), 1946.

The author describes his technic of retrograde abdominal aortograph}\ The patient is
sedated with a barbiturate the night before and morphine is administered one hour before the pro-
cedure. Prior to injection, the femoral artery is exposed by blunt dissection under local anes-
thesia at the level of the triangle of Scarpa and is punctured with a trochar l.S mm. in diameter,
through which injection of 50 c.c. of a 70 per cent solution of Diodrast is made in two and one-half
to three seconds. Tourniquets must be placed at the roots of both lower extremities in order to
produce a slowing of the circulation. The Trendelenburg position may be required in certain
cases. To avoid changes in pressure due to inertia and cardiac systole, the author uses a specially
designed pump with a piston which acts upon the embolus of the syringe. The piston works by
an air compressor with a regulator and a manometer. By this means 25 c.c. of the opaque solution
per second can be injected through the trochar, with a constant pressure of 15 pounds. The first
roentgenogram is taken when 40 c.c. of the opaque substance has been injected and the second
one immediately after completion of injection, using a fast plate changer. The trochar is with-
drawn when the injection is finished, and the adventitia of the artery and wound is closed.

By this method pathologic changes in the aorta and its branches can be clearly visualized and
studied. Roentgenograms are pre.scnted in ca.scs of atheromatous degeneration of the aorta and
iliac arteries, aneurysm of the abdominal .aorta, uterine fibroma, ovarian cyst, and visualization
of the renal circulation. By means of urograms taken at the same time, valuable information con-
cerning renal function is obtained, and thus a method of further study of renal pathologj' is
presented. The author hopes that retrograde abdominal aortography will become a common
method of clinical investigation and diagnosis. Serber.

Cook, "W. T., Cloakc, I*. C. P., Govan, A. D. T., and Collbeck, J. C.: Temporal Arteritis:

A Generalized Vascular Disease. Quart. J. Med. 15:45 (Jan.), 1946.

The thesis is presented that there exists in elderly people a widespread arterial disease, not
uncommon but rarely recognized, in which characteristic arterial and striking local signs occur.
The inflammatory and degenerative changes in the walls of the affected arteries produce a charac-
teristic histologic picture. The case histories of seven such patients with temporal arteritis are
presented. The symptoms and signs in this group, together with those from the thirty-one cases
reported in the literature, are described.

The characteristic clinical features are anorexia, loss of weight, joint and muscle pains,
pyrexia, painful arterial thrombosis, and severe headaches, occurring in elderly patients. At
least one-half the patients so far reported have had visual disturbances leading in many instances
to complete loss of sight. Post-mortem examination was carried out in two cases. A charac-
teristic histological picture was noted in the aorta and in the temporal, radial, subclavian, femoral,
coronary, renal, retinal, coeliac, and mesenteric arteries. Involvement of the femoral vein was
found in one case.

The pathological features are those of a subacute inflammation spreading probably by the
vasa vasorum to the media. The internal clastic lamina appears to cause the inflammation to
spread longitudinally. The lamina may be destroyed and in the process of healing, new redupli-
cated layers are formed. The intima becomes hypertrophied and thrombosis is a common sequel.
Pathologically the vascular disease differs from thromboangiitis obliterans and periarteritis
nodosa.

The prognosis is relatively good as regards life, though it may be fatal in some cases. Though
the generalized character of the disease is emphasized, the term temporal arteritis has been retained
as indicating a specific clinical entity in the absence of any definite etiological factor.

Naidk.

SELECTED ABSTRACTS

407

Faust, F. L.; Repeated Sympathetic Blocks; Their Limitation and Value. Anesthesi-
ology 7:161 (March)', 1946.

The value and limitation of repeated sympathetic blocks are emphasized. This form of
therapy is useful in diseases of the arterial and venous systems, particularly in acute and chronic
thrombophlebitis, post-traumatic dystrophies, traumatic shock associated with a crushing wound
of an extremity, various inflammatory processes, herpes zoster, and joint stiffness. The technics
of lumbar and cervical blocks are described. Naide.

Weeks, p. M., Steiner, A., and Victor, J.: Splenorenopexy in Essential Hypertension.
Surgery 19:515 (April), 1946.

Splenorenopexy in the dog with bilateral constriction of the renal arteries produces a collateral
circulation from the spleen to the capillaries about the convoluted tubules of the renal cortex.
A reduction in blood pressure occurs in hypertensive dogs following splenorenopexy. It was
therefore decided to test the effects of splenorenopexy in patients with essential hypertension.
The operation was performed on three patients aged twenty-four, thirtj^ and thirty-two years,
respectively. The cut edge of the spleen was apposed to the cut surface of the kidney.

The results were uniform. In none of the patients with hypertension was the blood pressure
reduced for more than three weeks. This patient was seriously ill at the time with pulmonarj'
embolism and infarction. The other two showed a fall in blood pressure onlj'’ during the
operation .

It was concluded that splenorenopexy had no significant effect on the blood pressure of three
patients with essential hypertension. Naide.

Pratt, G. IT.: Traumatic Aneurysms of the Extremities. Am. J. Surg. 71:743 (June), 1946.

Five aneurysms of the lower extremities, the result of gunshot wounds, were present in 450
wounded men. A tendency to massive hemorrhage was characteristic and in itself was an indica-
tion for operation. As a result of the author’s experience, the following suggestions were made
relative to the management of such patients: Where possible, the operation should be postponed
for three to six months to permit adequate collateral circulation to develop, but where the wound
is open or infected, delay Is dangerous. Operation in such instances should be performed at the
earliest opportunit}^ where adequate instruments and surgical personnel are available. Two
tourniquets should accompany transportation of such patients and should be applied, in event of
severe hemorrhage, above and below the site of bleeding. Sympathetic ner\'e blocks are an
important part of therapy and may mean the difference between success and failure in the surgical
treatment. Where plastic operation on the artery has been done, the anti-coagulants heparin and
dicumarol are necessary and should be continued until the outcome is no longer in doubt. After
operative recovery, these patients should be treated like those with obliterative arterial disease,
with emphasis on the development of collateral circulation and care to prevent injury or infection
of the part. Naide.

Blalock, A.; Effects of an Artificial Ductus Arteriosus on Experimental Cyanosis and

Anoxemia. Arch, Surg. 52:247 (March), 1946,

Experimental studies were performed in an effort to determine whether the creation of an
artificial ductus arteriosus would be helpful in the treatment of pulmonarj’’ stenosis or atresia in
patients. Attempts to produce the desired degree of pulmonary stenosis were unsuccessful.
It was then decided to attempt to produce unsaturation of the arterial blood by the removal of
pulmonary tissue combined with the creation of a pulmonary arteriovenous fistula. This was
finally done successfully by the removal of lobes of one or both lungs and the anastomosis of the
severed proximal ends of the pulmonary artery’ and vein of these lobes. This resulted in a high
degree of arterial oxygen unsaturation because some venous blood returned to the heart without
having passed through pulmonary capillaries. An artificial ductus arteriosus was created by anas-
tomosing the proximal end of the divided left subclavian artery to the side of the left pulmonary

408

A^IERICAN UEART JOURNAL

artery in four of the experiments. In two dogs, the end of the innominate arterj' was anastomosed
to the side of the right pulmonarj' artery. The creation of an artificial ductus arteriosus under
these conditions usually resulted in an increase in the oxygen saturation of the arterial blood. The
results of these studies strengthened the impression of Doctor Taussig that the patient with pul-
monary stenosis would be improved if the pulmonarj' blood flow were increased and led to the
development of the operation that is now performed on patients with pulmonary stenosis or
atresia. Naide.

Gregorj', R., Levin, W. C., Ross, G. T.. and Bennett, A.: Studies on Hypertension:

VI. Effect of Lowering the Blood Prc.ssurcs of Hypertensive Patients by High

Spinal Anesthesia 'on the Renal Function ns Measured by Inultn and DiudrasI

Clearance. Arch. Int. Med. 77;3S.S (April), 1946.

The common therapeutic practice of attempting to lower the blood pressure of hypertensive
patients made it advisable to determine whether such lowering of the blood pressure has any ad
verse influence. In view of the relationship of arterial pressure to renal filtration, the frequency
with which hypertensive states are associated with pathologic changes, and the associated abnor-
malities which might influence arteriolar renal blood flow, it seemed especially desirable to deter-
mine whether therapeutically induced significant falls in blood pressure would affect renal function.

The methods used by these authors were as follows- inulin and diodrast clearances were de-
termined as a control and after high spinal anesthesia was induced. This procedure was studied
in ten patients with essential hypertension and in two patients with chronic glomerulonephritis.
A significant fall in inulin and diodrast clearances was observed to occur in cverj- instance in which
the blood pressure fell significantly and remained low for as long as fifteen minutes. It was also
obsen-ed that the degree of decrease in inulin and diodrast clearances was roughly proportional
to the amount and duration of the fall of the blood pressure. That the decrease in clearance ^'aIues
was caused by the drop in blood pressure was shown by the following data: fl) The clearance
values invariably rose toward the normal control levels during the second experimental hour when
the blood pressure had risen toward or to the control level; (2) in several patients in whom the
blood pressure remained low for two hours, the inulin and diodrast clearances remained propor-
tionally low. In one patient in whom there was no fall in blood pressure although sensory paralysis
had reached the second interspace, with complete motor paralysis of the lower extremities, there
was a slight unexplained rise in pressure and a definite increase in clearance values.

The authors further emphasize that the correlation between the fall in blood pressure and
the diminution in Inulin and diodrast clearances occurs in patients with either normal or impaired
renal function. Thej’’ conclude that the results of this study necessitate a clinical appraisal of the
effect on renal function of anj- therapeutic effort which aims at symptomatic lowering of the
blood pressure in patients with hypertension. Bellet.

McDowall, R. J. S.t The Stirrmlaling Action of .Acetylcholine on the Heart. J. Physiol.

104:392 (April), 1946.

Acetylcholine injected into the isolated perfused hearts of cats, rabbits, and rats causes slow-
ing and weakening of the heart beat which is almost invariably followed by an increase in rate and
strength of the heart beat. Atropine abolishes the initial inhibitory effect of acetylcholine and,
usually, the secondary acceleratorj’ effect so that the only effect of acetylcholine after atropiniza-
tion is a more forceable systolic contraction.. Eserine enhances and ergotoxine abolishes or re-
verses the stimulating action of acetylcholine on the atropinized heart. After paralysis of the
cardiac autonomic ganglia by nicotine, acetylcholine still e-xerts its stimulant effect; it must act,
therefore, directly upon the cardiac muscle. After section of the A-V bundle, acetylcholine causes
only a slight initial inhibitorj^ effect upon the ventricle, followed by the usual stimulating effect.

On the basis of these data it is reasoned that the increased force of ventricular-contraction
during vagal slowing is not only a function of the cardiac muscle In accordance with Starling’s
Law of the Heart, but also a direct effect of the released acetylcholine on ventricular muscle.

pRIEDLAKn.

Book Reviews

ELECTROCARDiOGRArHY: By Louis N. Katz, A.B., M.A., M.D., F.A.C.P. Lea & Febiger,

Philadelphia, 1946, ed. 2.

, This is theisecond edition of a well-known book and many obvious changes have been made
in both text and illustrations. There are 825 pages with 525 excellent illustrations, a considerable
increase over the previous edition. The paper stock is high grade and there are few,' if any, typo-
graphical errors.

The author has changed his views on several subjects such as the range of the normal electro-
cardiogram and the nature of the shortened P-R, prolonged QRS syndrome. In the previous
edition the precordial leads were limited to CFj and CFj, while this edition includes CFs.

Most beginners will find this book extremely complex, but an effort toward simplification
has been made by listing the salient diagnostic points of each condition in concise fashion. Ad-
vanced students will find a wealth of material for study, although there may be a few controversial
points which are treated according to the view's of the author.

There are certain subjects W'hich, while not of great importance, are inadequately treated.
Because this is a comprehensive text, it seems unfortunate that short sections w'ere not devoted
to such subjects as an analysis of the various types of precordial leads and especially V leads.
There is also inadequate discussion of e.\'tremity potentials and the esophageal lead.

Those w'ho have used the first edition of this book w'ill find the present edition familiar but
w’ith many improv'ements. Those w'ho are unfamiliar with the ivork wdll find it a very satis-
factory and comprehensive treatise. In a field which is expanding and changing as rapidly as
electrocardiography, it is obviously a Herculean task to produce such a book. Readers will find
it superior to most texts in this field. Scott Butterworth.

Exercises in Electrocardiographic Interpretation: By Louis N. Katz, A.B., M.A., M.D.,

F.A.C.P. Lea & Febiger, Philadelphia, 1946, ed. 2.

This book is a companion volume to the author's text on Electrocardiography. It includes
100 cases illustrated with 166 electrocardiograms and brief case histories. A number of new cases
have been substituted in this edition and the total number of cases has been expanded from 90
to 100.

It is obviously difficult in selecting cases for a volume of this type to be comprehensive, but
the author has selected a variety of types which cover the more common electrocardiographic
variants and abnormalities, and he has wisely omitted complex or controversial cases. All of
the electrocardiograms include Leads CFj and CF^ in addition to the limb leads, and most also
have CFs, An attempt has been made to include normal variants to illustrate the changes due
to the position of the heart in the chest and other factors.

Embryo cardiologists will find this a very helpful book for training themselves in interpreta-
tion of “unknowns.” More advanced students w'ill find it a stimulating review' which will allow'
them to study the view's and interpretations of the author carefully. Scott Butterw'orth.

409

American Heart Association, Inc.

1790 RnoAinvAY at SStii Stri:i:t, Nkw YotiK, N. Y.

Dr. Hoy W. Scott
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Vice-President

Dk. CnoRoi: K. Hi.hrmaks
Treasurer

Dr. Howard T1. Spragre
Sreretory

BOARD OF DIRFCTORS

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*Dr. Wileiam H. Bhsk
Dr. Cl.ARKScn DR EA ClIAt'E

*Dr. Tinsery R. Harrison
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*Dr. H. M. M.arvin
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VtHinR.town, Ohio
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Boston
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♦Executive Committee.

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TelciiliolU'. Circlr S-SOOO

.■\nierican Heart Association is the only national organization devoted to
educational work reliiting to flisease.s of the heart. It.s artivitic.N arc under the
control and guidance of a Board of Direclor.s conipo-cd of thirty-three eminent phy-
•sicians who represent every portion of the country.

A central office is maintained for the coordination and ciistrihulion of important
information. From it tliere issues a steady stream of books, pamphlets, chart.s, films,
lantern slides, and similar educational materia! concerned with liie recognition, pre-
vention, or treatment of diseases of the heart, which arc noTv the leading cause of death
in the United States. The ,\mj:rican Heart Jopryai, is under the editorial super-
vision of the .Association.

The Section for the Sttidx' of the I’eriphcral Circulation was organized in 1935
for the purpose of stimulating interest in investigation of all types of diseases of the
blood and lymph vessels and of problems concerning the circulation of blood and lymph.
Any physician or investigator may become a member of the section after election to
the American Heart .Association and payment of dues to that organization.

The income from membership and donations provides the sole financial support
of the Association. Lack of adequate funds seriously hampers more intensive edu-
cational activity and the support of important investigative work.

Annual membership is S5.00. Journal membership at $11.00 includes a j'ear’s
subscription to the .-American Heart Journ.m. (Janiiary-Dccember) and annual mem-
bership in the As.sociation. The Journal alone is $10.00 per year.

The Association earnestly solicits your support and suggestions for its work.
Membership application blanks will be sent on request. Donations will be gratefully
received and promptly acknowledged.

-110

American Heart Journal

VoL. 32

October, 1946

No. 4

Original Communications

THE RELATION BETWEEN CIRCULATION TIME AND THE AMOUNT
OF THE RESIDUAL BLOOD OF THE HEART

B. Gernandt, M.D., and G. Nylin, M.D,

Stockholm, Sweden

T he introduction of determinations of circulation times has afforded the
clinician assistance in diagnosis, prognosis, and management. A number of
important studies have been published on this subject. Blumgart and Weiss^
injected radium C intravenously and, with Geiger-M tiller tubes, were able to
determine the time when the injected substance arrived in different parts of the
vascular system. The advantage of this method was that an objective determina-
tion of the time interval was obtained. Weiss was able to demonstrate a retarda-
tion, as compared with the normal, in patients with cardiovascular disease. In
cases of cardiac insufficiency, it was observed that the protraction of the circula-
tion time was, to a certain extent, proportional to the degree of insufficiency.

Winternitz and his co-workers* injected sodium aurodecholate into the vena
cubiti and determined the time required for the patient to notice a bitter taste
on his tongue. In spite of the fact that the patient's subjective cooperation is
necessary, the inaccuracy of this method is surprisingly small, as results which
were in very good agreement were obtained in repeated experiments on the same
patient.

Employing Winternitz 's method, Tarr, Oppenheimer, and Sager^ found the
normal circulation time to be 10 to 16 seconds with a mean value of 13 seconds,
reckoning from the instant when the injection was given until the patient noticed
the first taste sensation. For “compensated heart patients,” Tarr found a
moderate prolongation of tlie circulation time, and for the “decompensated
patients” he found a considerable prolongation.

From Medical Department II. the Sabbatsberg Hospital, Stockholm. Chief: Docent G, Nylin,

M.p;

Received for publication Jan. S.'S, 194(1.

411

412

AMERICAN HEART JOURNAL

Malmstrom and Nylin,'' using decholin in 48 healthy persons, found that the
first taste sensation appeared after 8 to 21 seconds; the mean value was 12
seconds. The sensation persisted for periods varying from 7 to 24 seconds, the
mean being 12.8 seconds. The authors observed a decided relation between
the circulation time and the size of the heart (measured in accordance with the
method of Nylin, Lysholm, and co-workers'®) in patients with compensated
cardiovascular disease.

Nylin®-® earlier observed that the heart is subjected to considerable sudden
volume changes both under physiologic and pathologic condition&and that these
acute volume changes are due to variations in the amount of the residual blood.
He pointed out also that the circulation time is not only dependent on the degree
of insufficiency, but is also largely determined by the amount of the residual
blood. He found, too, that the heart volume is considerably larger in the
recumbent position than in an upright position, owing to the amount of the
residual blood. Simultaneously with this change in heart volume, Malmstrom
and Nylin^ observed a prolongation of the circulation time in the recumbent
position in comparison with that in the upright position.

Nylin'-'® employed G. de Hevesy’s method of labeling red blood corpuscles
and applied this method to the problem of the circulation time and the amount
of the residual blood. These investigations show that, however subjective the
method may be, the decholin method agrees on the whole with the objective
method in which labeled red blood corpuscles are used.

In the present study a more thorough investigation has been made of the
prolongation of the circulation time in the dilated heart due to the increased
amount of residual blood. In particular, the connection between the circulation
time and the heart volume has been studied, and the results have been handled
statistically.

The studies of Nylin and his co-wofkers have proved clearly that, above all,
the circulation time depends on the amount of the residual blood in the heart,
and only to a slight extent on the degree of decompensation, i.e., of congestion.
This relationship has not been pointed out previous^. The establishment of
this connection between circulation time and the amount of the residual blood
is not only of theoretical but also of important practical interest. Thus, it is
necessary to pay due attention to the varying amounts of residual blood in deter-
minations of the blood volume, and perhaps also in other investigations of the
blood flow.

The determination of the circulation time affords a possible method of
determining in a simple way whether or not the heart is dilated.

METHOD

Determinations of the circulation time and venous pressure were made on
patients under resting conditions. The patient, the upper part of whose bod}'^ was
bare, lay flat on his back on a bed from which the pillows had been removed.
A cannula with an inside diameter of 0.9 mm. was inserted into a cubital vein.
The cannula, which was heparinized, was connected with a fitting, in which an

GERNAXDT AND NYLIN: CIRCULATION TIME AND RESIDUAL BLOOD OF HEART 413

upright manometer tube was fixed. The measurement of the venous pressure
was made when the injection needle was oh a level with the central axillary
line. By means of slight pressure with the hand around the patient’s arm above
the cannula one could easily make sure whether the yenous pressure rose when
the arm was compressed and fell when the pressure was relaxed, and that there
was a free connection. Into the fitting, which was constructed as a three-way
tap, an injection syringe could be connected. By turning the three-way tap,
the injection syringe could be connected to the cannula.

In determinations of circulation times, 5 ml. of a 20 per cent decholin solution
was injected as quickl}' as possible. The time was taken from the instant the
syringe plunger reached the bottom. The patient then had to indicate when he
first perceived the sensation of a bitter taste, when it began to recede, and when
it had disappeared entirely.

The method has been previously described in detail and critically dis-
cussed by jMalmstrom and Nylin.^

The determinations of the heart volume were made in accordance with the
method worked out by L^^sholm', Nylin, and co-workers.’-* In healthy persons,
according to these authors, the normal mean value of the absolute heart volume
(Y) is 700 c.c. with a range of 457 to 945 cubic centimeters. The relative heart
volume (V/M.*), ,i.e., the volume expressed in cubic centimeters per square
meter of body surface, is, on the average, 370 c.c. with a range of 250 to 490 cubic
centimeters.

PRESENT INVESTIGATIONS

The material, which comprised 308 patients with heart disease, was divided
into ''compensated” and “decompensated” cases. The presence of decompensa-
tion was determined by general signs of congestion, such as palpable liver, palp-
able spleen, edema, roentgenologically demonstrable lung congestion. Roent-
genologic determinations of the heart volume, determinations of the circulation
time,. and measurements of the venous pressure were made on every patient.

Table I is a summary of the material, with calculations of the mean, standard
error of the mean, standard deviation, and coefficient of variation.

There is a clear correlation between both the absolute (\0 and the relative
(V/M.“) heart volume and the circulation time, with a correlation coefficient of
0.51 and 0.50, respectiveh^ (Table II and Fig. 1). There does not appear to
be any definite connection bemeen the heart volume or heart volume per square
meter of body surface and the \'enous pressure, as appears from the low correlation
coefficients shown in Table II. From Fig. 2 it is clear that, when the heart volume
increases from 350 to 900 c.c. per square meter of body surface in the compensated
cases, tlie rise in venous pressure is extremely slight. Consequently, the con-
clusion may be drawn that the circulation time is determined chiefly by the
heart volume, and therefore by the amount of the residual blood, and to a lesser
degree by the height of the venous pressure in tlie case of compensated heart dis-
ease. If a comparison is made of the relation between the absolute heart volume

414

AMERICAN HEART JOURNAL

Table I. The Heart Volume, Heart Volume per Square Meter of Body Surface, Venous
Pressure, and Circulation Time in Cases of Compensated and
Decompensated Heart Disease

number

1

i

M i

± CTm

S. D.

Compejisalei;

Heart volume in cubic centimeters (V) .

214

987.6

+ 23.3

1

±340.3

34.5

Heart volume in relation to the esti-
mated body surface (V/M.”)

202

568.7

+ 13.9

+197.3

34.7

Circulation time in seconds (first taste
sensation)

214

18.68

+ 0.53

+ 7.68 1

41.1

Venous pressure in centimeters

213

8.97

± 0.23

+ 3.39

37.8

Decompensated:

Heart volume in cubic centimeters (V) .

94

1,437.2

+55.3

+536.3

37.4

Heart volume in relation to the esti-
mated bodv surface (V/M.*)

93

832.5

+32.8

+316.3

38.0

Circulation time in seconds (first taste
sensation)

94

27.68

+ 1.27

+ 12.30

43.4

Venous pressure in centimeters

94

18.10

+ 0.65

+ 6.32

35.0

Table II. The Relation Between the Heart Volume in Cubic Centimeters and the
Circulation Time (the First Taste Sensation) in Seconds and Between
the Heart Volume and the Venous Pressure in Centimeters
IN Cases of Compensated Heart Disease

correlation

NU.MBER

r ± <tr

Compensated:

Volume (V) — circulation time

0.51 +.0.051

Volume (V) — ^venous pressure

0.16 + 0.067

Volnmp (V/M.2') — rirriilnflnn . .

202

0 50 + 0 053

Volume (V/M.“) — venous pressure.-

201

0.15 + 0.069

Circulation time — venous pressure

213

0.18 + 0.066

and the time from tlie moment of the injection to the last taste sensation instead
of, as before, to the first taste sensation, a correlation coefficient of 0.40 is found
(Table III), which indicates that here, too, there is a relation between the amount
of the residual blood and the length of the circulation time (determined by the
cessation of the taste sensation) in the compensated cases.

Table III. The Relation Between the Absolute Heart Volume and the Circulation
Time* and Between the Absolute Heart Volume and the Duration
OF THE Taste SENSATioNf

CORRELATION

NUMBER

r i Ct

Heart volume (V) — circulation time (last value)

— fUffpronr^* in rtrriilat:inn time *

198

198

-f0.40 + 0.060
+0.27 ± 0.066

♦The time from the moment of the injection to the disappearance of the bitter taste.
+The time between the first Rnd last taste sensations.

GERNANDT AND NYLIN; CIRCULATION TBIE ANI) RESIDUAL BLOOD OF HEART 415

If the time interv'al between the first and last taste sensation is calculated and
correlated with the heart volume, a correlation coefficient of only 0.27 is obtained.
From these investigations it appears that, for judging the relation between the
magnitude of the heart volume (and with it the amount of the residual blood)
and -the circulation time, the first taste sensation is the better guide.

^ C/rarfoion
fioe

Rig. 1. — The relation between the relative heart volume (V/M.2) and the circulation time In patients
with compensated and decompensated heart disease is shown. The patients were di'V’ided into groups
according to the heart volume, and each figure represents the mean figure for the values falling within a
class interval of 400 cubic centimeters. The chart was compiled from 202 cases of compensated and 93
cases of decompensated heart disease.

Venoui

preavre

man

Fig?.

, g. 2. — The relation between the relative heart volume (V/.M.2) and tho venous pressure in cases
of compensated and decompensated heart disease. The class divis'on of tho patients is the same as
that used In Fig. 1.

AMERICAN HEART JOURNAL

4Jf)

In the decompensated heart cases, there is a clear correlation between both
the absolute (V) and the relative (V/M.-) heart volume and the circulation time,
although it is less pronounced than in the compensated cases. The correlation
coefficients are 0.45 and 0.37 (Table IV and Fig. 1). This correlation is, however,
greater in reality than appears from the correlation coefficient, as the line which
represents the correlation is curved (Fig. 1).

Table IV. The Relation Between the Heart Volume in Cubic Centimeihrs and the
Circulation Time (First Taste Sens.vtion) in Seconds, and Between the Heart
Volume and Venous Pressure in Cases of Decompensated Heart Disease

correlation

NUMBER

r ± ffr

Decompensalcd:

Volume, rtg-.* (V)~ circulation time

Volume, rtg. (V)— venous pressure

Volume, rtg. (V/M.-) — circulation time.
Volume, rtg. (V/M.-) — ^\'enous pressure. .
Circulation tim.e — venous pressure

I

I

{

93

93

94

0.45 ± 0.082
0.36 ± 0.090
0.37 ± 0.090
0.37 ± 0 090
0.39 ± 0.088

*Rtg.=roentgouologic.

In comparison with cases of compensated heart disease, there is in cases of
decompensated heart disease a closer relation between the heart volume and the
venous pressure, as appears from the relati\-ely high correlation coefficient of
0.37 (Table IV and Fig. 2).

Table V. Tim Correl.vtion Between the Absolute Heart Volume aiid the Circulation
Timi?* and Between the Absolute Heart Volume and the
Duration of the Taste SensationI

CORREI^ITION

NUMBHR

1

r ± fr

Decojnpciisaled:

Volume (V) — circulation time (last value)

1

1

78

-fO.42 4- 0.093-

Volume (V) — difference in circulation time

78

i

-f0.21 ± 0.108

*Tiie time from the moment of Irijocdou to the {iisappcarancc of the bitter taste.

tThe time between the first and last taste sensations in cases of decompensated heart disease.

As in the compensated cases, there is also in the decompensated cases an
obvious correlation between the absolute heart volume and the time interval
between the moment of injection and the last taste sensation, with a correlation
coefficient of 0.42 (Table V). The duration of the taste sensation only gives a
correlation coefficient of 0.21.

SUMMARY

A statistical investigation on a considerable number of patients with both
compensated and decompensated heart disease as to the relation between the
size of the heart, the heart volume determined roentgenologically, and the circula-
tion time gives the following results:

GERNANDT AND NYLIN; CIRCULATION TIME AND RESIDUAL BLOOD OF HEART 417

In both compensated and decompensated heart disease there is a statistically
verified correlation between the heart volume, i.e,, the amount of the residual
blood, and the circulation time (first taste sensation). There is a similar correla-
tion between the heart volume and the circulation time (the last taste sensation).
The explanation of these two circumstances, which were first observed by Nylin,
is fouhd if it is assumed that the greater the amount of the residual blood in the
heart the longer .time it takes for the test substance injected to become mixed
with the residual blood and to reach the peripheral arterial system. Similarly,
the late disappearance of the bitter taste is explained bj’’ the fact that it takes
longer for the heart to pump out the test substance when the amount of the
residual blood is large, as in cases of dilated hearts.

These statistical results are in complete accord with Nylin’s experiences in
determining the circulation times by means of radioactive phosphorus.

The authors wish to express their gratitude to Professor G. Dahlberg of the Race Biological
Institute at Upsala for his kind assistance with the statistical studies.

REFERENCES

1. a. Blumgart, H. L., and Weiss, S.: Studies on Velocity of Blood Flow; Velocity of Blood

Flow in Normal Resting Individuals, and Critique of Method Used, J. Clin. Investi-
gation 4; 15, 1927.

b. Idem: Studies on Velocity of Blood Flow; Physiological and Pathological Significance
of Blood Flow, J. Clin. Investigation 4; 199, 1927.

c. Idem: Studies on Velocity of Blood Flow; Method of Collecting Active Deposits of
Radium and Its Preparation for Intravenous Injection, J. Clin. Investigation 4: 389,
1927.

d. Idem; Clinical Studies on Velocity of Blood Flow; Pulmonary Circulation Time,
Velocity of Venous Blood Flow to Heart, and Related Aspects of the Circulation in
Patients With Cardiovascular Disease, J. Clin. Investigation .5: 343, 1928.

e. Idem; Clinical Studies on Velocity of Blood Flow, Venous Pressure and Vital Capa-
city of Lungs in 50 Patients With Cardiovascular Disease Compared With Similar
Measurements in 50 Normal Persons, J. Clin. Investigation ,5: 379, 1928.

f. Idem: Clinical Studies on Velocity of Blood Flow; Pulmonary Circulation Time,
Minute Volume Blood Flow Through Lungs, and Quantity of Blood in Lungs, J. Clin.
Investigation 6: 103, 1928.

g. Idem: Studies on Velocity of Blood Flow; Circulation in Myxedema With Comparison

’ of Velocity of Blood Flow in Myxedema and Thyrotoxicosis, J. Clin. Investigation 9:

91, 1930.

2. Winlernitz, M., Deutsch, J., and Briill, Z.; Fine Klinisch brauchbare Bestimmungsmethode
der Blutumslaufszeit mittels Dechoiininjektion. (Kurze Mitteilung), Med. Klin. 27: 986,
1931.

3. Tarr, L., Oppenheimer, B. S., and Sager, R. V.: The Circulation Time in Various Clinical
Conditions Determined by the Use of Sodium Dehydrocholate, Am. Heart J. 8: 766, 1933.

4. Malstrom, G., and Nylin. G.; Weitere Untersuchungen iiber die Bedeutung der verianger-
ten Kreislaufzeit fiir die Kardiologie, Cardiologia 5: 333, 1942.

5. Nylin, G., Sallstriim, T., and Agrcn, O.: Physiologische und pathologische Herzvolumen-
schwankungen, Verhandl. d. deutsch. Gesellsch. f. Kreislaufforsch. 12: 369, 1939.

6. Nylin, G. : Relation Between Heart Volume in Recumbent and Erect Positions, Skandinav.
Arch. f. Physiol. 69: 237, 1934.

7. a. Nylin, G., and Malm, M.; _ Ueber die Konzentration von mit radioaktivem Phosphor

markierten . Erythrocyten ini Arterienblut nach der Intraven5sen Injektion solcher
Blutkorperchen, Cardiologia 7: 153, 1943.

b. Nylin, G., and Malm, M.: Concentration of Red Blood Corpuscles Containing Labeled
Phosphorus Compounds in Arterial Blood .After Intravenous Injection; Preliminarv
Report, Am. J. M. Sc. 207: 743, 1944.

418

AMERICAN HEART JOURNAL

8 Nylin, G.; The Dilution Curve of Activity in Arterial Blood After Intravenous Injection
of Labeled Corpuscles, Am. Heart J. 30: 1, 1945.

9 Nylin, G.: Blood Volume Determinations With Radioactive Phosphorus, Brit. Heart J.
7; 81, 1945.

10. Nylin, G.; Arkiv for kemi, mineralogi och geologi, Bd. 20 A, Nr. 17, sid. 1, 1945. (Kungl.
Vetenskapsakademien.)

11. Nylin, G.: On the Amount of, and Changes in, the Residual Blood of the Heart, Am.
Heart J. 2.5: 598, 1943.

12. Lysholm, E., Nylin, G, and Quarna, K.: Relation Between Heart Volume and Stroke
Volume Under Physiological and Pathological Conditions, Acta radiol. 1.5: 237, 1934.

13. Liljestrand, G, Lysholm, E., Nylin, G., and Zachrisson, C. G.; The Normal Heart Volume
in Man, Am. Heart J. 17: 406, 1939.

THE HEART IN PRIMARY SYSTEMIC AMYLOIDOSIS

Stuart Lindsay, M.D.

San Francisco, Calif.

T here is a large group of uncommon diseases, som.e systemic in nature,
in which involvement of the heart m.ay lead to cardiac failure.^® Few of
these^®"*® have been so delineated that their clinical, laboratory, and pathologic
sequences differentiate them easily from, the m.ore com.mon ty'^pes of cardiac
disease. By observation of certain peculiarities of their manifestations, and by
the recognition of the basic process or lesions in other tissues, one is not likely
to overlook the significance of certain of these generalized diseases which may be
accompanied by cardiac signs and symptoms.

Amyloidosis, particularly the primary systemic form of the disease, con-
stitutes one member of this group of miscellaneous, obscure cardiac diseases.
Weiss and co-workers^® have pointed out that an accurate etiologic classification
of these rare types of disease is mandatory, m.ainly because of the practical
importance of specific therapy. While no patients with primary amyloidosis
have recovered, none has received a form of therapy which appears to be effica-
cious in the secondary type of amyloidosis.'*'’®^

The purpose of the present report is (1) to summarize the clinical and
pathologic data available in the published reports of over forty cases of primary
systemic amyloidosis from the standpoint of clinical cardiac and systemic mani-
festations, aids in diagnosis, electrocardiographic records, and pathologic changes
in cardiac tissues; and (2) to record an additional case of primary amyloidosis
in which extensive, diffuse, myocardial, amyloid infiltration was responsible for
progressive cardiac failure and death.

CASE REPORT

First Admission. — h. S., — U47646, a married white woman, 59 years of age, the wife of a
clergyman, first entered the hospital on July 6, 1939.

Clinical History: For six months before entry she had noted increasing exertional dyspnea
and weakness. Three months before, edema of the ankles occurring at the end of the day ap-
peared. Three days before, she had first noticed substernal pain following moderate exertion.
An electrocardiogram, done four months before entry, showed a very low voltage and a moderate
left-axis deviation. Family and past history contained several significant items. Her father
died at the age of 72 years of peptic ulcer. Her mother’s death at the age of 75 years was due to
a cerebrovascular accident. The patient had two spontaneous abortions at two and three months.
The first was followed by an attack of "rheumatism,” which was relieved by uterine curettage.

From the Division of Pathologj-, University of California Metlical School.

Received for publication March 4, 1946.

419

420

AMIiRICAK UKAKT JOURNAI,

Migraine lu-aclaches, precipitated by tlic ingestion of eggs, liaci occurred since childhood. Her
three children had similar headaches. One year before, mild enlargement and pain in the knees
and .small joints of the hands occurred. These articular symptoms had persisted but were sta-
tionary.

Physical Examhwtion: The patient was an asthenic, well-nourished white woman. The
temperature was .37.4'’C.; pulse rate, 90; respirator}' ratc,24; weight, 53.6 kilograms (I IS pounds).
The head, eyes, ears, nose, and mouth were normal. When she was in the .sitting position, the
cervical veins were distended to a point 12 cm. above the second interspace. The left border of
the heart was 1.5 cm. to the left of the mid-clavicular line. There was no enlargement to the
right. A soft systolic murmur of moderate intensity could be heard .it the mitral and aortic
areas. The aortic second sound was hollow. There were occasional ventricular extrasystoles.
The blood pressure was 95, /60. 'riie lungs were clear throughout. Examination of the abdomen,
back, rectum, genitals, and nervous system showed nothing abnormal. There were obvious vari-
cose veins and slight pitting edema of both lower e.xtrcmities. The interphalangeal joints of both
hands were slightly widened, without any limit.ition of motion. Fluoroscopy of the chest showed
a diffuse enlargement of the heart, involving mainly the left ventricle and auricle. The right
side of the heart was enlarged to a lesser extent. The cardiac contractions were poor, and, at the
apex of the left ventricle, were almost absent, 'i'hc bronchovascular markings near the hilurn
of each lung were widened.

Lahorniory Examination: E.vamination of the blood gave the following data: hemogkhin,

85 per cent (12.3 Gm.); red blood cells, 4.5 million; white blood cells, 10,100, poK’inorphonuclear
leucocytes, 58.5 per cent (filamented, 48.5 per cent; nonlilamenled, 1C per cent); ecsinophiles,
2 per cent; basophiles, 0.5 per cent, lymphocytes, 32 per cent, monoetdes. 7 per cent. The er\'-
throcytes and platelets were normal. The scdiment.ation rate (Wintrobe) was 17 mm, (cel!
volume, 44 c.c. per cent; corrected rate, 20 mm.). Blood serum proteins; albumin, 3.61 per
cent ; globulin, 1.90 per cent; .albumin-globulin r.atio, 1.9. The urine contained a slight trace of
albumin. Tests for urobilin and urobilinogen were positive in undilut'-d urine but were negati\c
in dilutions of 1:20. No serologic tests for syphilis were done.

Gastric analysis with histamine showed a level of free hydrochloric acid reaching 48 degrees,
with the total acidity reaching 64 degrees. Pepsin and rennin were j^resent in the gastric juice.
The basal metabolic rate was —4 per cent.

.'\ clinical diagnosis of congestive cardiac failure due to coronary arteriosclerosis was made.
The patient's course was uneventful. She was advised to continue at home a regime of bed rests,
Galen B (the vitamin B complex from rice polishings), a high protein diet, and digitalis.

Second Admission . — The patient's second entry was on .August 17. 1939. One week before
admission an acute upper rcs])iratory infection with pain in the legs and back occurred. Shortly
thereafter she developed pain in the right lower che«t, accentuateti by respiratory movements.
Increasing dyspnea, palpitation, and slight cough and a temperature of 38.8’'C. appeared. There
w'as a slight increase in peripheral edema. These symptoms and findings were le.ss severe at the
time of entry into the hospital.

On admission, physical signs of a right pleural clTusion were found, and 5f)0 c.c. of sero-
sanguineous fluid were removed from the right pleural cavity. Its specific gravity was 1.016
and the Rivalta test was positive. No bacteria were present, and the sediment contained only
mcsothelial and red and white blood cells. The heart was still enlarged. The heart sounds were
the same as on previous examination. The cardiac rhythm was regular; the rate was 90.

Laboratory Examination: Examination of the blood gave the following data: hemoglobin,

86 per cent (12.5 Gm.); erythrocytes, 4.25 million; leucocytes, 9,930; polymorphonuclear leuco-
cytes, 55.5 per cent (filamented, 47.5 per cent ; nonfilamented, 8 per cent) ; eosinophiles, 3 per cent ;
basophiles, 0; lymphocytes, 3 1.5 per cent; monocytes, 10 per cent. The erythrocytes and plate-
lets were normal. Observed sedimentation rate, 37 mm. (cell volume. 41 c.c. per cent; corrected
rate, 34 mm.). The urine contained a moderate amount of albumin. Tests for urobilin and
urobilinogen were positive in an uiulilutVd specimen but were negative at 1:20 dilution. Blood
serum proteins: total, 6.4 mg. per cent; albumin, 4.08 mg. per cent; globulin, 2.32 mg. per cent;

421

LIXDSAY; HEART IN PRIMARY SYSTEMIC AMYLOIDOSIS

albumin-globulin ratio, 1.76. An electrocardiogram showed a rate of 93, ventricular premature
systoles, slight left-axis deviation, low-voltage QRS complexes, and low T waves in Leads I and

II (Fig. 1);

During the next twenty-six days, the amount of fluid in the right pleural cavity continued to
decrease. The sedimentation rate dropped to 27 mm. Despite almost complete bed rest and a
maintenance dose of digitalis of 1 dg. per day, the cardiac rate remained at about 90. Four
intravenous mercurial injections produced a good diuresis and prevented a gain in weight. The
intake of fluids and salt was restricted.

Third Admission . — The last entry in the hospital was on Nov. 13, 1939. While at home, the
patient had hot improved and had been bedridden. Six days before admission, the dyspnea
had increased. She had noted a constricting sensation in the thorax, with severe inspiratory,
bilateral thoracic pain. She became orthopneic and developed a low-grade fever. Four days
before admission, she became nauseated and began to vomit. Swelling of the face had been present
for some time but was more pronounced shortly before entering the hospital.

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1 — Electrocardiogram made on Aug. 1. 1930.

Physical Exaviiiiatioii* "llic toniperaturc was 38 C.; pulse rate, 90, rc^pirator\ rate, 26.
The patient was orthopneic and slightly cyanotic. There was edema of the face and ankles.
Abnormal venous distention of the neck was noted. The chest expanded poorly and there were
physical signs of fluid in both pleural cavities. The heart was enlarged to the left in the fifth
intercostal space. The sounds were poor. gallop rhythm was heared at the apex, and a sys-
tolic murmur was heard at the oartic area. The blood pre-ssure was 90/75. There was guarding
in the upper right quadrant of the abdomen and the liver was enlarged. Edema of the ankles
and sacral region was present.

Laboraiory Examination: E.xamination of the blood gave the following data: hemoglobin,
88 per cent (12.8 Gm.); red blood cells, 4.62 million; white blood cells, 12,600; polymorphonuclear
leucocytes, 65 per cent; lymphocytes, 25 per cent; monocytes, 10 per cent. The erythrocytes
and platelets were normal. The feces were normal. .\n electrocardiogram showed a rale of
lOO per minute, low voltage of the QRS complex, left -axis deviation, low Ti, T';, Ti, and T4, slight
elevations of S-’^D, and a small R4.

AMKKK AS ttrART JOURS' \1,

i’i2

CVi.rif,* Kinnov.'! t>? c c. f*f tliiul front Oir rijrht plt-itrnl cavity produccil little chunye
'n tit!’- p.itifatS ct>ndivion ulitcli rtniainf'd ptxir dnrintt tbe next two tteeks. She had frequent
•sf tack-’ of ndpra-rte rr-jth nauica and alKiominal di'tenliori. The heart sounds had a poor quality;
sher*- v.n~ ix t'aHnp rhythm tvith ttcfxasiona' ventrilnilar cxtra‘'\>tolfS. The rate continued at 100.
tit*' ccnical vein- v.ere titstencled ;5nd ptiKatinj:, :tn<l hepatic enlargement wjis progre.^sing. Ri-
li'tend iit.drot!iorax and edema of the face and legs tterc not relieved by mercurial injections and
atiiirtophyliine. During this period, lumbar puncture showed clear cerebro-pinal fluid, containing
lyntphocytc”. per cubic millimeter. The initial pressure was ISO mm. of water, anti the
Fantly, Lange, and Kahn test« gave normal findings.

On Xov. 30 , 5?39, the patient became >{nporou>; and was found to have a left flaccid hemi-
jiieria. Within ilsc next few day.s the deep rcfle.xcs on the left .side returned and .she became more
rt-sponsivt;. During the following three weeks, the muscular lone and voluntary movements on
the left sitle ificreaseti. though she remained confu-ed and disoriented, and had considerable difli'i-
cidtj' in speech.

The cardiac status slowly became wor^c. Pulmonary congestion became more pronounced.
Th»‘ pulse rate x'arieil between llOauti 130. and the respiratory rate, between 25 and 35. Several
epismlcs of Ciu-yne-Siokcs breathing responder! to amonoplulline. During the last three weeks
of life, there was a gradual elevation of temperature to a terminal level of 40.4® C. The edema of
the arms and h'gs was much more pronounced on the left hemiplegic side of the body for two
days before death. This dilicrence had no relation to position in bed. Death from cardiac failure
orcurred on Jan. 11, 1940, approximately one year following the onset of cardiac symptoms.

Aiilol’Sji litp'^rl . — The autopsy (i;..\ 40.5) was performed one and one-ltalf hours after death.
'I'here was m.ark'etl wasting of the subcutnneou.s fat and mu.sculature. The temporal and cervical
veins were distended and torluou.s. 'I'he abdomen w.as distended. There was edema of both
Itgs and arms, greater on the left side. The inter-phalangeal joints of the hands were slighly
I (il.argcd. The surface of the skin, the cyc.s, cars, nose, and mouth were normal.

The peritonea! cavity and each pleural cax-ity contained 1,000 c.c. of clear yellow fluid.
The heart w,'is eiilargctl. The left bonier e.\londed 11 cm. to the left of the niidlinc and the right
border 5 cm. to the right of the midline. Dense bilateral pleural fibrous adhesions were present.
Tile heart weiehed 500 Gm. I'ht serosal surfaces wore smooiii and glistening and had normally
distributed pericardial fat. .Ml of the. cardiac chambers were moderately dilated. There was
.inatomic patency of the foramen ovale. The vcniricular walls were hypertrophied, with the
left averaging 2.3 cm. in thicknc.ss and the right, 1 .3 cm. in thickness. The auricular walls varied
between 0,2 and 0.6 cm. in Ihickness. .Wl portions of the myocardium were unusually firm and
-filT: the auricular walls h.ail a leatliery consistenc}’. There was a pale brownish-tan pallor of the
entire rtnorardium. Tlirotigliout this layer, including the interventricular septum, trabeculae
c.'irrie.ac. and vent riadar papillary muscle.-, was a diffuse network of pale grayish-yellow, translucent
m.ateria!, tending tobc concentrated about vi.sible blood vessels and within the interstitial tissues.
Strong solution of iodine (U. S. R.) stained the myoairtiium diffusely, produeing a mahogany-
brown color, with the tr.insluccnl .areas t.aking the stain mor<‘ deeply (Fig. 2). The amyloid
infiltnition was most abimd.anl in the left ventriailar wall. Less .ibuiuiant infiltration had oc-
curreri in the epicardia! fat. The c.ardiac valvt's were not grossly altered. Tliere was a mild
translun-nt intimal thickening of the main coronary arteries, but these vessels had widely patent
lumen'-, an<i no .atheromnlmis lesions were present. No nodular amvioid deposits were encount-
ered in the heart. Both atiriadar appendages contained adherent ante-mortem thrombi.

The right lung weighed 30tl grams and the left lung weighed 340 grams. Both lungs were
p.a'^tiaUy atelectatic and mildly congested and edematous. The cut surface.s had a pale, pink,
glistening, inois't ajrpearance, and a rubbery consistency.

The liver weiglied l,080gr,ims, It.s parenchyma w.a*- brown in color, and tliere wa.s moderate
centra! lobular ronge-tion. A 1 cm. cavemou«. hemangioma lay bene.ilh the capsular .surface of
tile right lobe. The gall bladder svas rli-tendctl with Idle, hut its wall was normal. Tite spleen
Weighed lOgr.Tutw ami its cap-u!e wa- stnooih. The splenic pulp was firm, dark purple in color,
and xva- not hyperfilnstie. Scaticrcsl liiroughout wi-resmall 1 to 2 nun. 7ones of translucent, soft.
Anv.!aiii nuterial. The pulp ftained diflu-ely with strong solution of iodine (D. S, P.). The
di«cTrte amylmd mv-se-s stained a deepe? brown.

LINDSAW. HEART m PRIMARY SYSTEMIC AMYLOIDOSIS . 423

- Except for loss of distinct corticoinedullarj' differentiation, the kidneys were normal. The
pancreas and adrenal glands were grossly normal.

The ovaries, Fallopian tubes, and Uterus were atrophic. The uterine canal was lined by a
thin, pale, smooth endometrial layer. There was an unusual glistening pallor and translucency
of the inner half of the m3’ometrial layer.

Fig. 2. — Section of heart showing diffuse amyloid infiltration of myocardium and less abundant
deposition in the epicardium and endocardium (X 4/5). Stained -with strong solution of iodine (U. S. P.)
followed by acidified Eastman x-ray fixer. Photographed with red Wratten B filter Iso. 25.

Almost the entire muscular las'cr of the stomach, especially of the pyloric end, was thickened,
firm, and rubber3^ Extensive deposits of pale yellowish-gra\', translucent amyloid material lat-
between isolated muscle bundles. This muscular alteration was particularh' marked in and just
above the ptdoric sphincter. On the surface, the amj’loid deposits appeared as longi-
tudinal ridges and cords, visible through the transparent serosal la\'er. There was no gross evi-
dence of amyloid infiltration of the large and small bowel, but the outer muscular laj'cr of the
lower esophagus showed changes similar to those seen in the stomach. After fixation for several
da5’s in a solution of formaldehj'de (U. S. P.), the gastroentric amj’loid took on a brownish-purple
color but retained its shining, translucent characteristics. The cardiac amyloid did not show
this alteration.

The bone marrow of the lumbar spine was normal. A few small atheromatous plaques were
present in the intima of the aorta. There was no gross alteration of the superior or inferior
vena cava.

The entire right frontal lobe of the brain was pale, flattened, and soft. On section, this
frontal lobe, with the underlying basal nuclei, was almost entirely liquified. The superficial
layer of the cortex was relatively intact. The right anterior and right middle cerebral arteries

AMCRJCAN HiUKT JOUKXAI-

I !;■" J<!': nrtcTj ftirt- (XThtcIi-?! hi .inji-mortcin tliroinhi. 'I'hc pituitarj- and tluToul

<J/,i ! r. ir<

rf,

lu’fr
"'ih’-iTT-

-ffif Ta.e Ma‘N of iHsth lentriclf'- of (hf heart lia<! a siinilnr htstologic

Aian;, of tin- fat re!h of tih' <t:{»endoiv.rdin! laicr Iiad thickened eosinophilic cell
» htrh irai'r p't>:5ive jtatnin.: reaction' for ami Icid. Ail layers of the main roronary

- nrd tin- Jmdinin-'i/s'f! arttrie- and veins in thi* layer Here moderatoli infiltrated iWth
tO'iiiophilie amylffid material.

Tfirre was diffii-e interc'dlular ainyloM deposition in the tniocardinin (Fist- a). ‘I'he rna-
lay hitive. n indivhiual ntu'-miar cel!' and was continuous with amyloid infiltrating the
■..'Ivenritia o) bh^j i ve.seis and that 'iirrounding the endothelial wall of small capillaries. When
^l en in e.ro'.' scctiori, each myrs'ard.ial fiber i\a' encased in an amyloid ring, jtroducing a honey-
r.'«n:h appeatance, '1 he amount of intercellular amyloid v.-irictl in different parts of the myo-
r.irilitirn. Where it was mo't aliund.mt. the enelo'ed myocardial fiher.s were compressed, atro-
phied. grnniil.sr, anti liwgetier.ating. The oticlei were liistorted. Some libers had disappeared,
ItMving fti'iform sp.ict-' iti the amyloid matrix. Other libers were absent, leaving amyloid rings
which otrasionally cnntaim-rl small rlumps of eO'inofihilic debris and golden-brown pigment.
Some aricis showci! large amyloid sln-igs with no n-sidual myocardial fibers. El.sewhere in the
intef'ttti.if li''ne were ntHhiIar, snialf, roundeif amyloid depo.sits. Small lipid gfobules in main’
of the ih-generat ing muscle cells were revealed with the sinlan I\’ stain. For the most part, the
inter.'titia! amyloid was lioinogeneous, coinp.act. refractile: in some areas it was frayed and
iibriliary, ’i'he ami’lnid rings had largely replaced the pericellular reticulum fibers. By combin-
ing the T.-iJdl.aw connective tissue and Congo nil stains, it was noted 1 hat the remaining reticulum
filnrs ii'U.illy !a>' between llie mi'oeardial cell membrane and the pericellular annloid ring. Xo
rclltilar reaction to the amyloid hail nentm-d. and there was no acute miocardial nccrosi.s or
libro'is. 1 here was a greater di'gree of amyloiti infiliraliop in the left ventricle as compared to
the right. All the myocardial bhiod’ vessels, particularly the artcrie.s, contained rounded, con-
tinent amyloid depo-its. which centered in the medial layer with extension into the adventitia
(Fig. 4). few atrophic nuclei of tht- smooth muscle cells remained. None of the cardiac vessels
had sigtiificantly narrowed lumens. The interstitial, pericellular, and va.'cnlar amyloid distribu-
tion in e.tch auricle was similar to that seen in the ventricles. In addition, there were c.xtensivo,
rounded, irrejtular confluent amyloid nmsses in both the endocardial and pericardial layers, ’f'he
attricul.ar .append.age.- coiUainetl organizing thrombi.

All the cariliac valves had a similar histologic appearance. The valvular endothelitiin was
intact. Few connective tissue nuclei remained. The connective ti.'Stie fibers had lost their fibril-
lary ch.ar.icier and had become swollen, eosinophilir, and amorphous. In all valve.s were small,
irri gularli' rounded, rentmlly placed amyloid nodules.

Small amyloid ilejiosit;. were noted in the media and the intiina of the pulmonary artery.
■J'hc mctli.i of almost all of the niediuni-sized pulmon.iry arteries and vcin.s contained amyloid
nntcrial. l.c" abundant cleposits were present in the alveolar walls and in the snbinucosn of
the brie!chio!e.s. The alvetili were atelertaiir and many were linofl by large, cuboidal epithelial
rcHs. 'fhe aveolar wall-' slitnsetl a filirmis thickening in addition to that caused by the amyloid
infdlr.ition. Manv marrophages and fewer red and white blood cells lay in the alveolar spaces.

There wms motleratr central sinusoidal congestion of fhe hepatic lobules, hut llie parenchymal
Cells V, etc nut alter* d, Large amyloid di-posits were p.-'escnl in the fibrous .septa of the cavernous
hennngitima. Iniersliti.d infiltration of all the layers of the gall bladrier had occurn-d. The
fiiedi.j of the .arti-rie' wat similarlv involved.

The Malpighian bodies and much of the splenic pulp fmd been replaced by amyloid material.
Little was pre^ens in the walls of the renlm! arteries. In tlie pulp, the malerini lay betwi'en the
-itm'UHb, adjacent to the retinilo-endothelial cells lining the vascular crh.innebi,

'rhiff- was no .alte.ruion of the p.ancreaiic parenchyma. The medi.a of «ome of the mediom-
-i.'ctf {iffrriiM rofUaintvl .amiloirl deposits.

An orrasional renal gloinenilar tuft was distenderi with amyloid material. Tile convoluted
tubsil.'s v,rr*- flikated aiif! many contained albiinnn and desquamated epithelial cells.

A daiitisc annloid infihr.ition of the connective tissue «jf tlic myometrium and endometrium
- .-c si.-fti'-i f’Fiv 5). Tin- amyloid material in the uti-rus was moia- pale and filirillary th.m else-

LINDSAY: HEART IN PlilMARY SYSTEMIC AMYLOIDOSIS 425

Fig. 3. — Myocardium sho\nng pericellular amyloid rings, wth atrophy or absence of muscle fibers,

(X 120). Crystal \dolet stain.

Fig. -4. — Myocardial vein tvith amyloid infiltration of its ivall (X 2.70). Hematoxylin and cosin stain.

426

AM EKJGAN HEART J OUHNAL

FiK. 5. — Endometrium sliowinp interstitial amyloid IndltnUion (X 200). Hematoxylin and t-osin stain.

c. — Small arteries of adrenal capsule sliowlnK extensive amyloid
infiltration (X 2C0). Hemato.vylin and eosin stain.

, LINDSAY : HEART IN PRIMARY SYSTEMIC AI^IYLOIDOSIS 427

where. The media of the small and medium-sized arteries in the uterine wall contained amyloid
masse-s.'

Similar interstitial and vascular masses of amyloid were present in the ovar}' and cervix.
Minimal infiltration of the submucosa of the Fallopian tubes had occurred.

Amyloid deposition in the gastroenteric tract, including the esophagus, stomach, small bowel,
and colon, had an unusual distribution. While the normal outlines of the muscular bundles re-
mained, considerable atrophy or complete disappearance of many of the smooth muscle cells had
occurred. This muscular alteration was due to compression by narrow fusiform or ovoid inter-
cellular amyloid masses. Less abundant interstitial amyloid was present in the submucosa.
Bulky deposits were encountered in both the arteries and veins of the gastroenteric tract.

Almost identical muscular, vascular, and submucosal deposits of amyloid were present in the
urinary bladder.

. The aortic intima was widened and was composed largely of hyalinized collagen. Small
groups of lipid-containing macrophages were noted. Both the intimal and medial layers contained
small interstitial amyloid deposits. There was interstitial amyloid infiltration of the media of
the inferior vena cava. The bone marrow of the lumbar spine contained fat cells and hemopoietic
tissue in normal proportions. Erythrocytic, myelocytic, and megakaryocytic elements were
present in the usual numbers. Several small irregular amyloid deposits were noted. No plasma
cells were identified.

The pituitary gland was not significantly altered. The acini of the thyroid gland were larger
than normal and were distended with colloid substance. The cortical layer of the adrenal glands
was moderately hyperplastic and the cortical cells were well supplied with lipid material. Minimal
interstitial amyloid deposits were present in this layer. The medial layer of both the adrenal
and periadrenal arteries and veins contained masses of amyloid substance (Fig. 6).

The left internal carotid artery had a thin wall. The intima and much of the media were
the site of extensive atherosclerosis with calcification. The lumen contained a nonorganizing
thrombus. The internal elastic membrane had been partially destroyed. Small amyloid de-
posits were noted in the media.

The lumens of both the right antCA-ior and middle cerebral arteries were occluded by thrombi.
That of the former had undergone early organization while the thrombus in the latter vessel was'
corapleteh' organized and recanalized. Amyloid was absent in the.se vessels.

The entire right frontal lobe was infarcted and consisted of a cystic space limited externally
by the arachnoidal layer and posteriorly by a zone of gliosis. The cystic cavity contained a deli-
cate vascular and glial network infiltrated with lipid-filled macrophages. There were no amy-
loid deposits in the central nervous s\^tem or in its blood vessels.

The amyloid material in all situations stained distinctly with the Congo red, crystal violet,
and Mayer’s stains but did not react with the iodine stain.

COMMENT

Amyloidosis is a disease in which a foreign protein, amyloid, is produced and
deposited in certain tissues. Amyloid disease has been classified as follows y
(1) secondary amyloidosis; (2) primary amyloidosis; (3) amyloidosis associated
with multiple myeloma; (4) tumor-forming amyloidosis. The most common
form of amyloidosis is the secondary type which is ordinarily preceded by tuber-
culosis ‘or chronic suppurative disease, though less often may follow a non-
suppurative chronic inflammatory process. It has been shown that amyloid is
composed of two protein fractions and one polysaccharide fraction.^^’'*® The
vascular distribution of amyloid suggests that it may be deposited as a combina-
tion product, the result of a reaction between a fixed component of the vascular
wall and some component of the serum globulin.^'* Hyperglobulinemia may
occur with this reaction and the amyloid may represent tissue deposits of excess

428

AMERICAN HEART JOURNAL

globulin protein/'' Hyperglobulinemia and amyloidosis may occur together in
multiple myeloma. Of the cases of primary amyloidosis recorded in the litera-
ture, only five had absolute serum globulin levels over 2.2 per cent.'"’-'’^^-"^
It is probable that factors other than hj^perglobulinen ia are necessary for the
development of amyloidosis.''®

While the relationship of amyloid deposition to abnormal protein metabolism
in the secondary type of amyloidosis seems related to a bacterial antigen-antibody
reaction, this sequence is less clear in the so-called primary form of the disease.
Jaff6^'^ has stressed the relationship between the allergic state acquired during
a chronic infection and the appearance of amyloid substance, since secondary
amyloidosis is most frequently found in tuberculosis where the occurrence of
allergic reactions is so striking. Review of the histories in the published cases
of primary amyloidosis reveals a number with possible etiologic agents, including
past infections now quiescent,®’"’'-''*®’-® high protein diets,®"’®^ pyorrhea alveoiaris,®^
and mycotic infections.®' In the case reported in this paper, food allergy was a
possible etiologic agent. While hypersensitivity to foods or other ingested anti-
genic materials would suggest an etiologic basis for amyloid deposition due to an
antigen-antibody relationship, Rowe''® has seen no cases of amyloid disease in a
large series of allergic patients. It has been noted'*® that a high protein diet m.ay
produce hyperglobulinemia.

Primary systemic amyloidosis is rare but is now a well-recognized entity.
It differs from the more common secondary amyloidosis in several ways: (1) the
absence of specific etiologic factors such as tuberculosis or chronic suppurative
disease: (2) minimal or no deposition of amyloid in the liver, spleen, kidneys,
and adrenal glands, the sites of maximum deposition in the secondary type of
amyloid disease;, (3) maximum deposition in the heart, lungs, skin, mucous
membranes, striated muscles, and other tissues not usually involved in secondary
amyloidosis; (4) formation of nodular amjdoid tumors; (5) atypical reactions with
specific amyloid stains.®'®®

There may be difficulty in the clinical diagnosis of this type of amyloidosis
unless its fairly uniform signs and symptoms, characteristics, and distribution
in tissue are kept in view. Overlapping of the characteristics of the four types of
amyloid disease has been observed.

It is of interest to note that spontaneous amyloidosis in mice resembles
primary amyloidosis of human beings in its distribution, while the amyloidosis
produced in these animals by injections of sodium caseinate bears a resemblance
to the secondary form of the disease as seen in the human being.®®

To date, forty-four cases of primary systemic amyloidosis have been recorded
in the literature;'"®® forty of these have been summarized by Koletsky and
Steelier®® and by Lindsay and Knorp.®® Additional cases have since been re-
ported by Brown and Selzer®® and Golden.®® Cases recorded by Pick'® and by
Bannick and co-workers®® had been overlooked. Other papers dealing with
systemic and atypical amyloidosis, with cardiac involvement, have been listed''®'®'
in the Cumulative Index ]\Iedicus but due to war conditions are not available for
study. With the present recorded case, a total of forty-five cases with forty-three

LINDSAY: HEART IN PRIMARY SYSTEMIC AMYLOIDOSIS 429

autopsy reports are available for review. Two patients were alive at the time
the reports were made.

Of the forty-five cases, twenty-three showed clinical evidence of cardiac
failure during the course of the illness. In eighteen of the forty-three fatal cases,
it was stated that cardiac failure Avas the immediate cause of death. In one case
with extensive valvular deposits of amyloid, death due to cardiac failure was the
result of coronary atherosclerosis and myocardial infarction, though undoubtedly
the valvular amyloid contributed to cardiac failure before death. P'rom the
clinical and pathologic evidence available in the published cases, this author felt
that in fourteen patients death from myocardial failure was the result of cardiac
amyloid infiltration. In two additional instances, this possibility was likely,
though not definite. Of the forty-three fatal cases in which autopsies were done,
thirty-nine showed some degree of amyloid deposition in the heart. In a few
cases, the amyloid deposition was limited to small cardiac blood vessels.®’’’''’^
Clinical evidence of cardiac failure due to amyloid deposition in the heart
may be difficult to evaluate. Signs and symptoms suggesting cardiac disease
may be produced by amyloid involvement (1) of the lungs, with chronic cor
pulmonale, (2) of the trachea, or (3) of the mediastinum, or by the anemia which
often is present.’”’® Coronary atherosclerosis or hypertension may be complicat-
ing factors in the cardiac failure occurring in primary amyloid disease,

Amyloidosis may produce cardiac failure in several ways: (1) deposition
in the pulmonary vessels and alveolar walls with resulting chronic cor pulmonale;
(2) deposition in the cardiac blood vessels, including arteries, veins, and capil-
laries; (3) diffuse or localized nodular interstitial amyloid infiltration with or
without secondary degeneration of the myocardial fibers; (4) pericardial or
endocardial deposits; (5) e.xtensive valvular deposits producing stenosis or in-
sufficiency; (6) often a combination of several sites of deposition.

Review of the symptoms in many of the recorded cases of primary systemic
amyloidosis are those of cardiac insufficiency and insufficient blood flow to the
myocardium. These include dyspnea, cyanosis, weakness, precordial pain,
paroxysmal dyspnea, orthopnea, palpitation, and cough. Physical examination
has revealed edema, hydrothorax, ascites, cardiac enlargement, cardiac murmurs,
tachycardia, auricular fibrillation, venous engorgement and pulsation, gallop
rhythm, tick-tack sounds, and pulsus alternans.

The widespread systemic distribution of amyloid substance, with resulting
signs and symptoms, usually presents a bizarre, though somewhat uniform, clinical
picture. The sites of involvement and the systemic signs and symptoms in the
majority of cases have already been tabulated;®®’®® these may point to an amyloid,
background for the cardiac manifestations.

Lesions of the skin are fairly common. These have been described as
opalescent and papular,-’ opalescent, firm, and nodular,’® sclerodermic,®'’^’--
papular plus plaquelike scleroderma,’® weeping eczematous,®® and pink striae
beneath the nails of the fingers and toes.®® These deposits in the skin are, of
course, accessible for diagnostic biopsies. In the majority of cases where there
was an antemortem diagnosis, it was made bj'- this method from sites including the

m

AMERICAN HEART JOURNAL

buccal mucosa, skeletal muscles,'*’-'^ vagina, and stomach.^^ In
at least one instance^® amyloid in the tissues removed was not recognized. It
has been pointed out^" that, because of the variability of the staining reactions in
primary amyloidosis, tissue suspected of containing amyloid should be stained
with several of the known amyloid stains (Congo red, crystal violet, and iodine
and sulfuric acid).

Amyloid infiltration of the gastroenteric tract has been a frequent finding
in this group of cases and has led to the following symptoms and signs; diarrhea,
constipation, abdominal pain, nausea, vomiting, distention, intestinal hemor-
rhage, intestinal obstruction, epigastric tenderness, hematemesis, anorexia, and
postprandial pyrosis. In three cases gastric ulceration had occurred.

Enlargement of lymph nodes may be localized or, generalized and may result
in a localized amyloid tumor.^®

Enlargement of the tongue has been a frequent finding, often has suggested
neoplastic disease, and has been accompanied by dysphonia and dysphagia.
The buccal and nasal mucosa, the larynx, and the trachea have been sites of in-
filtration. Nasal hemorrhage'^® and laryngeal obstruction® have been described.
Facial rigidity has resulted from infiltration of the skin, subcutaneous tissues, and
muscles.^® Extensive involvement of skeletal muscle has produced the picture
of myotonia with an unusual degree of progressive fatigue and weakness. De-
posits in posterior roots, sympathetic ganglia, and peripheral nerves have resulted
in muscular weakness.^® Central nervous system involvement has not been
described.

Arthritis may be simulated, and involvement of bones, joints, and tendons
has led to limitztion of motion, disturbances in gait, and pathologic fractures,®®
Collapse®® or narrowing®® of vertebral bodies as the result of amyloid infiltration
has occurred. Purpura is a common symptom and is presumably due to amy-
loidosis of the blood vessels,®® though anemia and leucopenia resulting from
amyloidosis of the marrow®® suggests a thrombocytopenic basis for the bleeding
tendency.

In many cases involvement of small blood vessels, especially arterial, has
been widespread. Deposition in all portions of the genitourinary tract in both
men and women has been reported.

In addition to biopsy of accessible amyloid lesions, the intravenous Congo
red test may be helpful in establishing the diagnosis of amyloidosis. Bennhold’s
Congo red test®* has recently been evaluated by Stemmerman and Auerbach®® in
a large group of patients with secondary amyloidosis. These authors considered
-a 90 to 100 per cent absorption of dye as a positive test. Where only minimal
amounts of amyloid were present, false negative tests were likely to result.
False positive results occurred with technical errors and in the presence of renal
tubular damage. The Congo red test has been done in ten patients with primary
amyloidosis. In five of these,*®’®*’®®'®'*’®® the results were considered positive with
the percentage of intravenously administered Congo red absorbed from the blood
at one hour ranging from 60 to 100 per cent. In the five in whom the test was '
considered negative, *®’®®’®’’®®’®® the percentage of dyfe absorbed by the tissues

LINDSAY; HEART IN PRIMARY SYSTEMIC AMYLOIDOSIS 43r \

at one hour ranged from 0 to 35 per cent. In this small group of cases, there \vas
no apparent correlation between the amount of amyloid found at autopsy (or
estimated clinically) and the amount, of Congo red removed from the blood.
This test was not done in anj^ of those patients in whom amyloidosis of the heart,
was the cause of death.

In amyloidosis secondary to tuberculosis or chronic suppuration, the heart
is rarely involved, while the maximum deposition usually occurs in the spleen, ,
liver, kidneys, and adrenal glands. In fifty-seven tuberculous patients observed
post mortem, amyloid deposits in the heart were not encountered.®^ Amy-
loidosis is less common in chronic nonsuppurative disease, although in severe
rheumatoid arthritis amyloidosis has been reported in a few instances.®® In
experimental amyloidosis produced by injection of sodium caseinate, amyloidosis
of the heart was observed. There were perivascular deposits in the myocardium
and in the leaflets at the valves, particularly the mitral.'*'

Prim.ary amyloidosis is generally characterized by an atypical amyloid
distribution, often with cardiac involvement.®® In the forty-three available
autopsy reports, cardiac amyloidosis was encountered in thirty-nine instances.

In one case®^ the amyloid distribution was similar to that seen in the
secondary type of the disease. Conversely, several reports of secondary amy-
loidosis with the distribution characteristic of the primary type are available.

In Kann’s case ®® in which the amyloidosis presumably was secondary to syphilis,
there was extensive substitution of the myocardium by amyloid substance.
Both the auricular and ventricular walls were involved and there were nodular
deposits in the endocardium. Small amounts of amyloid were present in the
cardiac valves. Virchow®^ apparently was the first to observe amyloid deposition
in the heart. Not until 1907 was the cardiac distribution adequately described.

In eight patients with secondary amyloidosis, von Huebschmann®® found amyloid
in the connective tissues and blood vessels of the myocardium but rarely in the
valves or endocardium. None of the eight patients had cardiac manifestations. ■

More recently, other cases of cardiac amyloid, secondary to chronic suppura-
tive disease, have been reported. In Budd’s case ®® in which a prostatic adeno- .
carcinoma and urinary suppuration caused death, amyloid was encountered in
the small coronary blood vessles, myocardium, and endocardium. Only minimal
amounts of amyloid were present in the pulmonary and mitral valves.

In the case recorded by Spain and Barrett,®® amyloidosis secondary' to sup-
purative bronchiectasis was accompanied by amyloid deposits in the heart which
had produced clinical evidence of cardiac failure, including dyspnea, cyanosis,
edema of the legs, pleural effusion, and an increase in circulation time. The
electrocardiogram showed left-axis deviation and low 'Cmltage in all leads.

The visceral pericardium has often been one site of cardiac amyloid deposi-
tion in primary systemic amyloidosis. Nodular amyloid strata on this layer
have been described.^ Both small and large discrete amyloid nodules often are
present. In one case® both pericardial layers were firm and thickened. Gerstel*'*
described a grayish-gold, jellylike membrane on the surface of the heart. The :

. pericardial amyloid may take the form of small flecks*® or pearly-gray 1 mm.

432

AMERICAN HEART JOURNAL

nodules.^'’ In one case^® there were deep parallel grayish-yellow furrows in the
right auricular epicardium. At times the epicardium is thickened and grayish
yellow in color.®® In Kerwin’s first case, both pericardial layers were studded
with firm, translucent grayish 1 mm. nodules.®® The nodules were larger but
fewer in Golden’s case.®® In the pericardial laj'^er, the amyloid has had both a
vascular and an interstitial distribution. The latter has included amyloid rings
about thq pericardial fat cells in several of the recorded cases®’-*’®® and in the case
reported in this paper. These pericellular amyloid deposits have also been seen
in the periadrenal fat.®® Peters®® has pointed out that pericellular amyloid deposi-
tion may occur in many situations and has suggested that the deposition of amy-
loid on cell surfaces may be the initial process in amyloidosis. From the pub-
lished reports, it seems unlikely that amyloid in the pericardial layers has con-
tributed significantly to the production of cardiac failure.

The bulk of the cardiac amyloid has had a myocardial distribution in many
of the cases and is most important in the mechanism of cardiac failure. Both the
auricular and ventricular walls may be hypertrophied and thickened. When the
myocardial amyloid is diffusely distributed, these walls have been described as
hard or firm, pale, grayish tan or golden brown, waxy or translucent, homo-
geneous or glassy. The auricular walls are often stiff and leathery. The in-
volved myocardium tends to be rigid and resistant to cutting, and the chambers
retain their globular shape rather than collapsing. The diffuse myocardial amy-
loid deposits may appear as irregular, translucent,' pearly-gray or yellowish-
opaque streaks, gleaming flecks, or trabeculae or may be more localized as large
or small nodular masses, often projecting above the cut surface. One to 3 cm.
amyloid nodules have been noted in the ventricular walls.®®’®®

Microscopic examination of the myocardium in many cases has disclosed a
rather consistent pattern of distribution of the amyloid substance. The myo-
cardial blood vessels often contained mural amyloid deposits lying in any or all
of their layers. In a few instances, these have appeared in the main coronary
arteries. In one case, subendothelial amyloid at least contributed to narrowing
of the lumens of the main coronary arteries.®® More often, the medium-sized
and small coronary arteries were involved with distinct narrowing of the vessel
lumens. The veins, arterioles, and capillaries have also been the site of amyloid
infiltration. The marked degree of vascular narrowing associated with this
infiltration and the resulting diminution of blood flow to the myocardium has
undoubtedly been a significant factor in failure of the myocardium in many of the
cases.

Even more important in the mechanism of cardiac failure has been the diffuse
interstitial amjdoid infiltration of the myocardium. Aside from the deleterious
effects on the muscle cells, the extensive amyloid network must have interfered
greatly with the normal range of contraction and relaxation of the cardiac
chambers. In twenty of the cases it has been noted that narrow bands of amyloid
substance had been deposited about individual myocardial fibers appearing on
cross section as imprisoning rings or sheaths. At times, one portion of this
amyloid sheath may invaginate into the cytoplasm of the cell. The myocardial

LINDSAY: HEART IN PRIMARY SYSTEMIC AMYLOIDOSIS 433

fibers may be compressed, narrowed, or displaced and frequently have been
severely damaged. They were often atrophic, vacuolated, fragmented, necrotic, ■
or contained lipid or pigment deposits. Nuclear degeneration was common.
With excessive deposition, the muscle cells disappeared, leaving empty amyloid
rings or almost solid amyloid sheets. The fibers in those areas with less or no
amyloid often compensated by hypertrophy.

Beneke and Bonning^ were of the opinion that the amyloid material was
primarily deposited on and about the muscle cells. In the light of the observa-
tions of Peters,®® this may be true. Larsen," however, pointed out that the inter-,
cellular and pericapillarj'’ deposits were continuous and felt that the pericellular
amyloid originated in the blood vessels. This same continuity has been noted
by others®-'®^ and was seen in the case reported in this paper. The intercellular
amyloid appeared to e.xtend from extensive arterial and arteriolar deposits in
one instance.®'

KolleP® described the pericellular amyloid as being deposited in the peri-
mysium of the myocardial fibers. By combining the Congo red and a silver reti-
culum stain on the same .section, it was possible in the case reported in this paper
to demonstrate that the amyloid had largely replaced the pericellular reticulum
and, furthermore, that when the reticulum persisted, it lay between the cell
membrane and the pericellular amyloid ring.

Where the amyloid deposits were fewer and more localized, the material
lay in rounded, confluent, nodular masses, showing neither a distinct cellular nor
vascular origin.

In the majority of recorded cases, amyloid was present in the endocardial
layer, often as stratified or nodular deposits and occasionally continuous with the
myocardial amyloid. In one case®® where both valvular and mural endocardial
amyloid was particularly abundant, this material lay immediately beneath, the
endothelium. In many instances, the amyloid infiltrates mainly the deep endo-
cardial layers.

Of the forty-five cases of primary systemic amyloidosis, sixteen had amyloid
deposits in the cardiac valves. Valvular involvement is often slight and only
microscopically demonstrable. In a smaller number of cases, the valvular deposi-
tion was more striking. Discrete amyloid nodules, with thickening and rigidity
of several of the valves, have been described.^ Grayish-white 1-3 mm. 'discrete
nodules may be limited to the mitral valve. ^ In Roller’s case^® both the mitral
and tricuspid valves were hard, thickened, and stenotic. The valvular amyloid
in one instance appeared as grayish-red warty nodules on all valves except the
aortic.*® Fine shotty amyloid nodules were present along the free margins and
auricular surfaces of the mitral and tricuspid valves in the first case recorded by
Kerwin.®® In another case-® there was a plaquelike thickening of the line of closure
of the mitral valve. Amyloid nodules may lie both in the cusp and the annulus
fibrosis of the cardiac valves.®' In two of the recorded cases®®’®® there were un-
usually abundant amyloid masses in the cardiac valves. In Koletsky and
Stecher’s case®® all four valves showed nodular deposits of amyloid, particularly
in the aortic and mitral valves. These nodules had so involved the base and free

AMERICAN HEART JOURNAL

■iU

margins of the leaflets as to produce thickening, 'rigidity, immobility, and stenosis.
These authors explained the extensive involvement of the leaflets as a direct
extension of amyloid from the ring of the valve. All four valves were also ex-
tensively infiltrated with amyloid in the case recorded Lindsay and Knorp.^*^
In this instance, the valvular surfaces, particularly of the pulmonary and tricuspid
valves, were covered by smooth, nodular, glistening, translucent, yellowish-
white, soft amyloid substance, which had led to a distinct decreased mobility of
the cusps. The chordae tendineae were similarly covered, but their fibrous
structure was visible through the amyloid coating. In this case, the origin of the
amyloid from the adjacent endothelium was apparent. In both of these cases*®’^®
it was considered probable that the valvular amyloid infiltration played a signifi-
cant role in the mechanism of cardiac failure.

In addition to direct cardiac infiltration by amyloid material, cardiac failure
may also result from pulmonary amyloid disease. Chronic cor pulmonale with
right ventricular hypertrophy and dilatation on a pulmonary amyloid basis has
been recorded on several occasions^^’®^'®® and also was noted in the case reported
in this paper. The pulmonary amyloid infiltration in the case reported by Sap-
pington and co-workers®® was extreme. There was universal involvement of
both the arteries and veins plus almost complete amyloid infiltration of the alveolar
walls. Presumably the latter was related to capillary infiltration. There was a
marked reduction in the diameter of the lumens of the involved vessels, which
by interference with pulmonary blood flow had produced right ventricular
hypertrophy. A roentgenogram of the chest showed enlargement of the cardio-
vascular silhouette and an indefinite haziness of the lung fields. In one case”
some of the amyloid masses in the alveolar walls were so abundant as to cause
bulging of the alveolar epithelium into the acinar space. In the patient described
in this paper, there was also abundant pulmonary vascular and interstitial
amyloid which produced right ventricular hypertrophy and undoubtedly con-
tributed in part to the cardiac failure. Pearson and co-workers®® were of the
opinion that the obliterating pulmonary vascular amyloid infiltration in one of
their cases was a factor in the production of right ventricular failure.

Hypertension has been present in four of the recorded cases.®®’®®’®®’®' In the
first, hypertension was due to renal amyloidosis. In the second, gross renal
scarring and microscopic amyloid were present, but whether the two were re-
lated to each other and to the elevated blood pressure was not stated. In the
last two cases, renal amyloid was not present, and presumably the hypertension
was coincidental and essential in type. In one case®® the authors felt that cardiac
failure was the result, in part, of hypertension.

Electrocardiographic studies were done on twelve of the forty-five recorded
cases.®^’®®'^®’®*-®^’®® In nine of the twelve cases, myocardial amyloid infiltration
was considered to have been the cause of death. In six of these, low voltage in
the electrocardiographic record was a prominent feature. Katz®® has pointed
out that one cause of low voltage in the QRS complex is a diffuse myocardial
alteration which prevents a normal flow of current through the ventricular tissues..
The myocardial amyloid in this group of patients appears to have produced a

LINDSAY: HEART IN PRIMARY SYSTEMIC AMYLOIDOSIS .435

ciistinct conduction disturbance in the ventricular walls. In one case’^ the P-R
interval was slightly prolonged. Alteration of the P wave was not noted in any
of the cases. Auricular fibrillation was present in one case/^ and ventricular,
premature contractions were noted in two cases. Axis deviation was more often ;
to the left than to the right. In one case with an abnormal electrocardiogram,
the responsible rnyocardial lesion was due to arteriosclerosis and not amyloid.’’’®

Treatment of primary systemic amyloidosis to date has been symptomatic,
expectant, and directed toward the complications. In only twelve cases has. an
ante-mortem diagnosis been made, usually by biopsy. The rate of progress of
the disease is variable. Duration of life from the onset of symptoms has varied
from four months’® to fourteen years^® and sixteen years.®^

It is well known that recovery from secondary amyloidosis may occur, usually
following retrogresrion of the responsible inflammatory process. Trasoff and ,
co-workers®® have cited some twenty-nine instances of recovery recorded since
1880. Experimental amyloidosis in mice produced by protein administration .
has receded when such treatment was terminated.®*’®® Reabsorption of experi-
mentally produced splenic amyloid appeared to be the result of leucocytic and , .
capillary invasion, amyloid fragmentation, and foreign body giant cell activity.'*®
Grayzel and co-workers®® found that administration of liver substance either
resulted in absorption or delay in deposition of experimentally induced amyloid
in mice. These studies have led to successful therapy of secondary human
amyloidosis.^’ Despite the continuation of the underlying process, thirteen
children with chronic suppurative disease were treated orally with powdered
whole liver extract. With the exception of four dying with advanced tuber-
culosis, this group showed marked improvement or complete recovery from amy- ,
loid disease. Early signs of recovery were diminution in size of the liver and ;
spleen, with the other signs and symptoms regressing more slowly. It was em- ;
phasized that the recovery rate was not regularly progressive, suggesting a variable,
chemical composition of the amyloid substance.

More recently Jacobi and Grayzel®" recorded the effects of the oral adminis-
tration of 4 to 8 Gm. of desiccated powdered whole liver preparation to patients
with amyloidosis secondary to tuberculosis. Treatment was continued for a
year or more, and of sixteen patients, nine were cured as demonstrated by the .
disappearance of symptoms and the absence of Congo red retention.

While there are undoubtedly certain differences in the composition of .
amyloid in the primary and secondary forms of the disease, therapy with liver
■substance may be found to be of benefit in the primary type.

Clinical and laboratory recognition of primary amyloidosis, further elucida-.
tion of .the responsible mechanisms at work, M’ith their subsequent removal or
amelioration, may result in recovery as in e.xperimental and secondar>- amyloid-:
osis. Accumulating evidence suggests that the fundamental disturbance is
identical in all types of amyloid disease and that when the basic mechanism is
known, primary amyloidosis will be classified as a "secondary” type.

436

AMERICAN HEATIT JOURNAL

SUMMARY

1. A case of primary systemic amj'-loidosis is reported. The duration
of the illness was one year. Death was due to cardiac failure, the result of
extensive amyloid infiltration of the myocardium.

2. There are now forty-five cases of primary systemic amyloidosis recorded
in the literature. These have been reviewed, and their cardiac manifestations
and involvement bj' amyloid substance have been summarized and discussed.

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LINDSAY : HEART IN PRIMARY SYSTEMIC AMYLOIDOSIS 437

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SOME OBSERVATIONS ON THE PATHOGENESIS OF
• EDEMA IN CARDIAC FAILURE

Francis Reichsman, M.D., and Harold Grant, M.D.

Dallas, Texas

T he pathogenesis of cardiac edema has been the subject of extensive investi-
gation and many explanations have been given. The classical work of
Starling'- cleared up much of the confusion which had existed in the theories
of the pathogenesis of all forms of edema. At present the most widely accepted
explanation is that cardiac edema is due to an increase in the filtration of water
and electrolytes through the capillaries into the extracellular space secondary
to a rise in the hydrostatic pressure within the capillaries and elevated venous
pressure. The rise in venous pressure is caused -by failure of the right heart.
The absence of edema in left heart failure and in peripheral circulatory^ failure is
good evidence that circulatory retardation is not an important factor. -

Krogh, Landis, and Turner® have shown that in experimental venous
congestion the rate of edema formation is increased as the colloidal osmotic
pressure is decreased. Many patients with congestive heart failure have slightly
decreased plasma proteins, though the levels reached are very'- rarely low enough
to explain in itself the formation of edema. Warren and Stead'® and Bram-
kamp' have shown that cardiac edema fluid does not contain an increased amount
of protein. This is good eAfidence that increased capillary permeability is not
a significant factor.

In patients with congestive heart failure the urinary output is low and no
satisfactory explanation of this has yet been given. Several observers®-® have
demonstrated that there is an increased blood volume and hemodilution in
congestive heart failure rather than the lowered blood volume and hemocon-
centration which would be expected if the oliguria were a manifestation of the
increased transudation of water into the extracellular space. Fremont-Smith''
showed that following the ingestion of water, normal subjects had less hemodilu-
tion and more diuresis than patients with cardiac edema. Thus one has to assume
that there is also a renal factor in cardiac edema. Futcher and Schroeder® further
confirmed this idea by demonstrating impairment in the ability of the kidneys to
excrete injected sodium chloride in four patients convalescing from severe con-
gestive heart failure.

From the Departmcni of Medicine of the Southwestern Medical College and the Parkland
Hospital.

.Vided by grants from the John and Mary MarRle Foundation and from the DAZTAN Foundation.
Received for pulillcation March 1. 1010

438

REICHSMAN AND GRANT: PATHOGENESIS OF EDEMA IN CARDIAC FAILURE / 4,39 :

In. 1944 a paper w^s published which aroused much comment and interest
and in ho small part gave rise to the study which is reported here. Warren and
Stead^® gave excess sodium chloride to two patients just after they had become
compensated following a bout of severe congestive heart failure. They reported
that both of the subjects showed a significant weight gain before the venous
pressure rose. As a result of this experiment they offered the following explana- 4
tion of the mechanism of cardiac edema : “Edema develops in chronic dongestive l
failure because the kidneys do not excretd salt and water in a normal manner.
This disturbance in renal function is related to the decreased cardiac output and
not to engorgement of the kidneys from an increased venous pressure because the
salt and water retention may occur before there is a rise in venous pressure.”

In our study, we have attempted to see also whether the venous pressure or the
weight rose first as a patient went into cardiac decompensation; but instead of ;
adding excess salt to induce failure, digitalis was withdrawn.

The Effect oj Withdrawing Digitalis on Venous Pressure and Edema Formation . — Observations
were made on three patients with clinically inactive rheumatic heart disease and chronic auricular .
fibrillation. Two of the patients (N. C. and L. B.) had both aortic and mitral valvular lesions, ,
while the third (B. H.) had mitral stenosis and insufficiency. All three of the subjects had had .
repeated episodes of cardiac decompensation, with both left and right heart failure. In two of
them .peripheral edema had been present, while in the third (N. C.) no clinically detectable edema
but marked enlargement of the liver and elevated venous pressure was observed during the '
periods of right heart failure. ;

When admitted to the hospital the patients were suffering from chronic heart failure of a
' moderate degree. Cardiac compensation was achieved by the use of digitalis and a diet which
contained approximately 3 to 4 Gm. of sodium chloride a day. .Absolute bed rest was not ■
enforced, the patients being allowed a moderate amount of activity.

The venous pressure was measured in the basal state by the direct method, the level of the ■ ^

right auricule being estimated to be at a level 10 cm. above the back.® The apical rate and the
pulse rate were counted, and then the patient's weight was measured.

When clinical evidence and laboratory tests showed that cardiac compensation had been-
.restored, cardiac failure was induced by omitting digitalis medication. Determinations of the' .
venous pressure and of the weight were continued as during the control period.

The data obtained are listed in Table I and Fig. 1. Our results show that
after the discontinuance of digitalis a considerable rise of venous pressure (approx-
■ imately 60, 55, 85 mm. of water) occurred with no or very slight gain in weight.

In Patient N. C. there was even a loss of weight which undoubtedly was due to ,
the fact that he started to vomit a few hours before the termination of the ex-
periment. The largest weight gain, 0.8 kilogram, occurred in Patient L. B.

In this patient the venous pressure, after a considerable rise, fell spontaneously.
Consequently a general diet was substituted for the salt-poor diet, which repre-
sented an increase of approximately 5 Gm. of sodium chloride a day. Following
this change the venous pressure rose from 122 to 215 mm. of water during the ;
next five days, while the patient’s weight increased by only 0.9 kilogram. . Dur-
ing the next four days the patient gained another 1.9 kilograms, while the venous
pressure remained essentially unchanged. Onl}'^ after this period did very slight
pretibial edema appear.

440

AMERICAN HEART JOURNAL

Table I. The Effects of Stopping Digitalis in Three Patients With Heart Failure

VENOUS

PATIENT

DATE

WEIGHT

PRESSURE

apical

R.-VDIAL

REMARKS

(KG.)

(mm. of water)

RATE

RATE

B. H.

3/16

54.5

76

62

62

3/17

53.9

82

3/18

54.4

86

68

68

Taken oft digitalis

3/19

53.7

3/20

54.0

105

72

3/21

54.5

106

3/22

54.0

105

70

3/23

3/24

54.6

144

74 1

54.7

137

At 10 P.M. onset of fast au-

1

ricular fibrillation and left
heart failure; digitalized

X. C.

4/19

52.8

120

64

64

4/20

53.3

117

57

57

4/22

Taken oH digitalis

4/24

4/25

53.5

140

64

64

53.1

145

4/26

53.5

120

71

71

4/27

53.3

140

72

72

4/28

53.2

131

67

67

j

4/29

.53.3

150

88

84

1

4/30

52.2

173

Vomiting; liver enlarged;

digitalized

5/1

51.7

83

80

1

80

L. B.

6/22

40.3

89

60

60

6/23

40.3

82

45

45

Taken off digitalis

6/25

40.4

95

62

62

6/26

40.0

108

64

64

6/27

40.0

108

62

62

6/29

40.3

124

58

58

6/30

40.4

124

58

58

7/1

40.7

132

58

58

7/2

41.1

170

60

60

7/4

165

62

62

7/6

40.9

150

58

58

7/8

41.2

155

60

60

7/10

41.2

153

60

60

7/13

40.8

140

58

58

7/20

40.5

122

60

60

7/22 put on general diet

7/23

40.9

152

60

60

7/25

41.2

171

62

62

7/27

41.4

215

68

68

42.8

220

82

78

8/1

43.3

210

92

78

Moist rales over lung bases;

slight pretibial edema; di-
gitalized

It seems quite clear that when digitalis is withdrawn the first change noted
is a rise in venous pressure before there is any significant weight gain. The three
subjects all were patients with mitral stenosis and auricular fibrillation, and the
objection may be raised that the sequence of events observed holds true only for
patients with similar abnormalities. If this were true, we would have to formu-
late a different explanation of cardiac failure in each separate type of heart
disease.

REIGHSMAN AND GRANT; PATHOGENESIS OF EDEMA IN CARDIAC FAILURE 44]

The data presented by Warren and Stead’^ are open to some criticism. Their
first patient was started on salt at a time when his hematocrit reading was 54
to 55. It seems quite possible that this patient was dehydrated. When his
salt intake was increased and diuretics omitted, the hematocrit reading fell.
After an hematocrit reading of 46 was reached, the weight and venous pressure
rose simultaneously. The weight gained at the onset of the experiment may
well have been the result of replacement of water and salt in a dehydrated person.
In their second patient, the amount of weight gained before rise in venous pressure
was 2.6 kilograms, since the first venous pressure reading recorded after this
weight level was reached showed a rise from, 40 to 150 mm,, of water.

Pig — Changes in venous pressure and weight during development of cardiac failure.

Futcher and Schroeder^ in their experiments on the excretion of injected hyper-
tonic sodium chloride in patients who had been in congestive heart failure studied
also the changes in venous pressure. Of their five cases studied, adequate venous
pressure readings were made on three patients. Of these, only two are suitable
for discussion here because the venous pressure was at an abnormal level in the
third patient at the onset of the experiment. In the first patient twenty-four
hours after the administration of 33 Gm. of sodium chloride the venous pressure
had risen 50 mm. of water (125 to 175) without weight gain. The second patient
showed a rise in venous pressure of 43 mm. of water (115 to 158) and a weight
gain of 1.5 kilograms twenty-four hours after the injection of 24 Gm. of sodium
chloride. Thus we see that both of these patients studied by Futcher and
Schroeder® had a rise in venous pressure to abnormal levels with little or no weight
gain.

442

AMERICAN HEART JOURNAE

L. B., our third subject, also showed a marked rise in venous pressure
before gain in weight after salt had been added to her diet.

These observations are quite compatible with the backward failure hypoth-
esis' according to which cardiac edema is due mainly to the increased venous
pressure secondary to right heart failure.

CONCLUSIONS

1. As cardiac decompensation develops after the withdrawal of digitalis,
the rise in venous pressure precedes the gain in weight and the formation of edema.

2. The main factor in the production of cardiac edema-is the increase in
venous pressure.

The authors are deeply indebted to Dr. Tinslcj' R. Harrison for his guidance and suggestions
throughout this study.

REFERENCES

1. Bramkanip, R. G.; The Protein Content of Subcutaneous Edema Fluid in Heart Disease,
J. Clin. Investigation 14: 34, 1935.

2. Fishberg, A. M.: Heart Failure, Philadelphia, 1940, Lea & Febiger.

3. Fremont-Smith, F.: Mechanism of Edema Formation, New England J. Med. 206; 1286,
1932.

4. Fremont-Smith, F.; The Mechanism of Water Diuresis in Man, Proc. Soc. Clin. Investi-
gation 9: 7, 1930.

5. Futcher, P. H., and Schroeder, H. A.; Studies on Congestive Heart Failure. II. Im-
paired Renal Excretion of Sodium Chloride, Am. J. M. Sc. 204: 52, 1942.

6. Gibson, J. G., Jr., and Evans, W. A.: Clinical Studies of the Blood Volume. III. Changes
in Blood Volume, Venous Pressure, and Blood Veolcity Rate in Chronic Congestive Heart
Failure, J. Clin. Investigation 16; 851, 1937.

7. Harrison, T, R.: Failure of the Circulation, ed. 2, Baltimore, 1939, Williams & Wilkins Co.

8. Kennedy, J. A., Lyons, R. H., and Burwell, C. S.: Measurement of \’enous Pressure by
Direct Method, Am. Heart J. 16; 675, 1938.

9. Krogh, A., Landis, E. M., and Turner, A. H,: Movement of Fluid Through Human Capil-
lary Wall in Relation to Venous Pressure and Colloidal Osmotic Pressure of Blood, J. Clin.
Investigation 11; 63, 1932.

10. Payne, S. A., and Peters, J. P : Plasma Proteins in Relation to Blood Hydration; Serum
Proteins in Heart Disease, J, Clin. Investigation 11; 103, 1932.

11. Smirk, F. H.: Observations on the Causes of Edema in Congestive Heart Failure, Clin.
Sc. 2; 317, 1936.

12. Starling, E. H.: On the Absorption of Fluids From the Connective Tissue Spaces, J. Physiol.
19: 312, 1896.

13. Stead, E. A., Jr., and Warren, J. V.; The Protein Content of the Extracellular Fluid in
Normal Subjects After Venous Congestion and in Patients With Cardiac Failure, Anoxemia,
and Fever, J. Clin. Investigation 2.3; 283, 1944.

14. Thomson, W. A. R.: Plasma Proteins in Cardiac Edema, Quart. J. Med. 3; 587, 1934.

15. Warren, J. V., and Stead, E. A., Jr.: Fluid Dvnamics in Chronic Congestive Heart Failure,
Arch. Int. Med. 73; 138, 1944.

CORONARY SINUS RHYTHM
David Scherf, M.D., and Raymond Harris, M.D.

New York, N. Y.

TT IS now generally accepted that stimuli originating in the auriculoventricular
^ node may produce three patterns of cardiac rhythm. In the first type the
pacemaker is situated in the upper part of the auriculoventricular node, and a
normal or slightly shortened P-R interval occurs. In the second type the focus
of origin is in the center of the node and both auricle and ventricle contract
simultaneously. In the third type the stimulus originates in the lower part of
the . auriculoventricular node and the auricle is activated after the ventricle.
Electrocardiograms imitating these three forms of auriculoventricular rhythm
may also be found with the same focus of origin in the presence of conduction
disturbances from the auriculoventricular node to the auricle or ventricle.’®'-®
, . In the era before electrocardiography, the existence of auriculoventricular
rhythm with a normal P-R interval caused much confusion. The appearance
of normal auriculoventricular succession following extirpation of the sinus node
even led some authors to assume that the sinus node was not the only pacemaker
in the auricle under normal conditions. Later it was shown that, with an elec-
trocardiogram exhibiting deeply inverted P waves in Leads II and III and a nor-
mal or only slightly shortened P-R interval, the focus of origin of the stimulus
was situated in the upper part of the auriculoventricular node which extends to
the sinus of the coronary vein. This rhythm was called coronary sinus rhythm.®®
This type of disturbance is still not too well known and has not yet been studied
on an extensive basis.

In this paper we are reporting our obser\'*ations on thirty-one patients with
coronary sinus rhythm studied over a period of six years. The data obtained
in our thirty-one cases are reproduced in Table 1.

OBSERVATIONS

Incidence . — Between the 3 ^ears 1940 and 1945, inclusive, 23,610 electro-
cardiograms were taken at the Metropolitan Hospital where they were routine
on the medical service. This figure includes many instances in which tracings
were obtained repeatedly from the same patient. During this period, the electro-
cardiographic pattern of coronary sinus rhythm was observ’^ed in thirty-one
patients, of which seventeen were men and fourteen were women. These

From the Medical Department of the New York Me<licail GoIIesie, Metropolitan Hospital Service.

- IJeceiv«Kl for publication March 23. 1940.

^43

Tahi-e I. Clinical and Electrocardiograimiic Findings in Thirty-one Patients With Coronary Sinus IIhvtiim

R. D. 16 Low Deeply Deeply — Observation 71 0.12 0.14 Normal

. ncg. ncg.

J. R. M 22 Low Neg. Ncg. — Keratitis 63 O.Il 0.14 Normal

G. W. F 52 Low Deeply Deeply — Deeply Hypertension 110 0.08 — Left ventricular strain

neg. neg. neg. pattern

Tadlic I. CrjNrcAL and ELECTiiocARDroGRAPinc Findings in Thirty-one Patients With Coronary Sinus Rhythm — Cont'd

•SCHERF AND HARRIS: CORONARY SINUS RHYTHM 447,

figures do. not permit calculation of the true incidence of coronar\> sinus rhythm,
but they do permit the conclusion that the condition is not as rare as was formerlj',
believed. In another series of 10,000 cases, an auriculoventricular nodal rhythm
was found in forty-five patients. Fifteen of these showed coronary^ sinus rhythm.-'*
The incidence of coronary sinus rhythm is, therefore, approximately the same in
these two series.

Electrocardiographic Pattern . — For many years, the form of the P waves in
tracings of auriculoventricular rhythm was merely mentioned as being negative,
and even in the classic monographs by Lewis'® and by \\^enckebach and Winter-
berg^s the form of the P waves in all three standard leads was not discussed.

It is now established that in auriculoventricular nodal rhythm the P wave
in Lead I is low, positive, and sometimes invisible, while in Leads II and III
it is negative.^® In this paper are included only those tracings which show such P,
waves. Electrocardiograms with a positive P wave in Lead I, an inverted P
wave in Lead III, and an isoelectric P wave in Lead II are not included since in
these cases we are usually dealing with a regular sinus rhythm.

Another characteristic of the P waves frequently found in Leads II and III
is their very sharpty peaked form. Even when they have a duration of 0.05
second, the P waves seem shorter because they are so pointed. In the majority
of our cases, we could hot find the form showing a steep downstroke and a slow
upstroke described as characteristic by Lewis.'® In the chest leads (CRo and
GR4) the form of the P waves usually resembles that found in Leads II and III,
but diphasic as well as positive P waves were also observed.

In cases of coronary sinus rhythm the electrical axis of the auricle points,
to the left and the depolarization of the auricle proceeds in a direction opposite
to that occurring under normal conditions.'"'-'

The electrocardiogram reproduced in Fig. 1, obtained from a patient with
syphilitic aortitis and involvement of the coronary artery orifices, shows P waves
that are positive in Lead I and sharply inverted in Leads II, III, and CR4.
The P-R interval measures 0.11 second. There is moderate right-axis deviation.
The abnormal depression of the S-T segment is partly due to digitalis treatment.

With slight variations, the P wave pattern described previously was seen
in all cases. In seventeen tracings, the sharp pointing was present. The P
waves in a case of mitral stenosis were markedly widened, but even here the
negative pointing in Leads II and III was present despite the intra-auricular
conduction disturbance.

The P-R interval during coronary sinus rhythm varied between 0.08 and
0.17 second. Tracings with a P-R interval of less than 0.08 second were not in-
cluded in this investigation. In one case the P-R inten^al during coronary sinus
rhythm was 0.17 second, and during regular sinus rhythm it was 0.20 second
(Case 1, Table I). In fourteen electrocardiograms the P-R interval during cor-
onar>' sinus rhythm measured between 0.10 and 0.12 second. In thirteen cases
it was possible to compare in the same individual the P-R interval during regular
sinus rhythm with that found during coronary sinus rhythm.. The difference
between both values ranged from 0.0 to 0.08 second. In three patients the.

P-R interval was found to
in evaluating these figures
inter\^al during auriculoven
of the stimulus formation c
the speed of conduction fr
ventricle.

Fig. 1. — Coronary s

The heart rate during
beats per minute. No rela
length of the P-R interval.

Evidence of myocardi
twenty-three patients. In
The electrocardiogram was

Condition of the Heat
was present in twenty-fou
observed. Marked abnon

ge was lo
lese patien
n eicht oa

SCHERF AND HARRIS: CORONARY SINUS RHYTHM

449

ment, or other signs in the other eleven patients indicated the presence of an
abnormal heart usually due to coronary sclerosis. In some elderly patients or
in patients with pneumonia, the presence of organic changes in the heart was
possible despite normal clinical findings. The heart was presumably normal on
clinical and electrocardiographic examinations in only three subjects (Cases 5,
8, and 9, Table I).

In connection with our data, it is worthy of emphasis that Ruskin and his
associates found ten patients with definite evidence of heart disease among fifteen
cases of coronary sinus rhythm.-® Hj'-pertension was present in eight of the ten
cases. In another series of twelve patients with different types of auriculoven-
tricular nodal rhythm, seven showed hypertension.®

Response to Exercise, Amyl Nitrite Inhalation, aftd Carotid Sinus Pressure . —
One feature of the coronary sinus rhythm is its lability. Capable of changing
spontaneously, coronary sinus rhythm may frequently also be converted easily
into regular sinus rhythm by exercise, amyl nitrite inhalation, or carotid sinus
pressure. This change, of course, is possible only in those cases where the sinus
node still functions. In some cases exercise or inhalation of amyl nitrite simply
causes acceleration of the e.xisting coronary sinus rhythm (Table I); in others,
these, measures cause the sinus rhythm to become so accelerated that it gains the
upper hand and displaces the coronary sinus rhythm. The results cannot be
predicted because they depend on the degree of acceleration of either node.

Similarly, pressure on the right or left carotid sinus may only slow the
existing coronar}^ sinus rhythm or change either rhythm into the other. In
Fig. 2 is shown the effect of right carotid pressure in Lead III of the electro-
cardiogram on a patient who displayed coronary sinus rhythm spontaneously
on many occasions. The rate was slowed; one beat with an abnormal P wave
presumably was caused by one part of the auricle being activated by the sinus
node and another part by the auriculoventricular node; then pure coronary sinus
rhythm followed. Once established, this abnormal rhythm often persisted for a
long time with a rate frequently the same as that of the regular sinus rhythm pre-
ceding the carotid pressure.

In Fig. 3 is shown a spontaneous change in Lead II from coronary sinus
rhythm to regular sinus rhythm and back to coronary' sinus rhythm. In many
instances the changes, resembling the sudden ending of a paroxysmal tachy-
cardia, are as abrupt as in the beginning of Fig. 3.

Sinus Escape. — During auriculoventricular rhythm in dogs caused by cooling
of the sinus node, an “escape” of the sinus node in the form of normal beats with
normal P waves and normal P-R interv^als Avas observ^ed occasionally.”’^® Some
of these tracings were explained in a different way,®® but a sinus escape undoubt-
edly occurs. We were able to observe it in the electrocardiograms of three
patients.

t'ig. 3 . — Lead 11. Spontaneous change from coronary sinus rhythm to sinus rhythm and back to

coronary sinus rhythm.

— : . , . , , . SCHERF AND HARRIS; CORONARY SINUS RHYTHM - 4o'i'

FiSr 4 was . obtained from Case 1, Table I. A left bundle branch block is
present and the P waves show the typical sharp inversion in Leads II and HI.

. Lead II, as well as in CR 2 , slightly premature beats with normal P waves and
somewhat longei P-R intervals occasionally appear. Their interpretation as
sinus escape beats seems justified.

Fjg. 4. — Coronary sinus rhythm with .sinus escape in Leads II and CR 2-

: ' , DISCUSSION

• The diagnosis of coronary sinus rhythm in tracings like those of Figs. 1 to 4
is supported by the result of anatomic and e.xperimental investigations. Ana-
tomic observations reveal data compatible with the assumption that the coronar>"
sinus area is occasionally the site of stimulus formation. In his classic treatise,
Tawara described specific fibers which, enter the posterior part of the auriculo-
ventriciilar node from the sinus of the coronary vein.-' The characteristic struc-

452

AMERICAN HEART JOURNAL

lure of tlie specific fibers near the coronary sinus in the calf Avas described by
Aschoff who was reminded of a third stimulus center in addition to the sinus and
auriculoventricular nodal centers. -

The specific muscle fibers of the auricle which originallj'^ formed one unit
are later separated into two parts, one which represents the sinus node, and a
second Avhich unites Avith the auriculoA'^entricular node to form its auricular por-
tion.^ Tlie peculiar structure of the coronary sinus fibers Avas also stressed by
others."’’- Kung described a small bundle of muscle fibersentering theauriculo-
A'entricular node from the area of the coronarA’^ sinus. This bundle contained
many ganglion cells AA’hich in seA'eral places AA'ere in direct contact AAuth the
muscle fibers. A netAA'ork of nerA^e fibers also surrounded the muscle fibers.
From these findings, the author concluded that these structures apparently
possessed a remarkable functional ability.'-

Experimental AA'ork shoAA’ed that AA-arming of the coronary sinus area in dogs
caused a tachycardia Avith a normal P-R interA’^al.^” In dogs exhibiting electro-
cardiograms AA’ith inA'erted P aa'ua^cs preceding the QRS complex by a normal
distance, the area of primary negatiA it}'^ (the focus of stimulus formation) has
been found to be in the coroaary sinus area by direct leads.’" In the experiments
by Zahn, hoAveA^er, only smoked paper tracings AA'ere used, and doubts Avere ex-
pressed concerning the results of his experiments and the studies of Meek and
Eyster.’"* Therefore, the experiments of Zahn AA^ere repeated Avith the aid of the
electrocardiogram. It could be shoAAm that a regular tachycardia Avith deeply
inA^erted P AvaA^es and normal P-R interA'als occurred during the Avarming of the
coronary sinus area through the AA'all of the coronary A’ein or inferior caA'al A'^ein
in the dog heart in situ.

Since an electrocardiogram AA'ith three limb leads obtained in such an ex-
periment has neA^er been reproduced to our knoAAdedge, one of these experiments
may be described here. Fig. 5 AA^as obtained from a dog Aveighing 4.45 kilograms.
During artificial respiration, the chest AA'all and pericardium Avere opened under
nembutal and morphine anesthesia. The apical area of the heart Avas slightly
lifted from its pericardial bed and a thermode AA^as applied through the Avail of
the inferior caA'^al A’^ein to the area around the orifice of the coronary sinus.

Lead I, obtained after discontinuation of the AA’arming of the coronary
sinus, shoAA’s in the beginning a tachycardia caused by the Avarming of the coronary
sinus area. The P AvaA^es are not clearly visible because they are Ioav. With
sloAving of the heart rate, sinus rhythm Avith normal positive P Avaves recurs.
Lead II, registered during the tachycardia, shoAA's deeply inverted P AA'aves fol-
loAved by positiA'e Ta aa’^ua'^cs and preceding the QRS complex by about 0.11
second. The tracing of Lead III, as in Lead I, AA^as obtained after discontinuation
of the Avarming process. In the first half of the tracing, deeply inverted P AvaAi^es
precede the QRS complex, but in the second half regular sinus rhythm recurs
Avilh high positive P AA'^aves and inverted Ta AA-aves.

In all experiments, the same pattern of P AvaA'es Avas obtained as in the
clinical tracings. In Lead I the P AAmve AA-as invisible or Ioav positiA'^e; in Leads II
and III it Aims deeply iin^erted and usually sharply peaked.

SCHERF AND HARRIS : CORONARY SINUS RHYTHM

453

In our opinion, coronary sinus rh 3 ''thm is actually not as rare as it is often
believed to be; then too, it is frequently overlooked. That inverted P waves
appear under normal conditions in Lead III is known but when the}^ were also
found in Lead II, the^’- were often not attributed to a new rhythm but rather ex-
plained by summation according to the Einthoven rule. Some authorities'
diagnose auficuloventricular rh^^thm even with isoelectric P waves in Lead II.
For this study we accepted only cases with definitelj'^ inverted P waves in Leads
II and III. In doubtful cases it will be of help to -know that coronarj’- sinus
rhythm is extremely variable and that spontaneously, or with carotid pressure,
or exercise, it changes readily into sinus rhythm.

Fig. a . — Coronary sinus rhythm produced experimentally in the dog. For
description of the three limb Ictids, see text.

Onh^ twice during, the observation period of six years did we find the form
of auficuloventricular rhythm with inverted P waves between QRS and T;
that is, auficuloventricular rhythm originating in the lower node. Both times,
this rhythm was temporary. Auficuloventricular rhythm without visible P
waves, usually attributed to a stimulus originating in the middle of the auriculo-
ventricular node, was seen only nine times. These results differ from those of
other writers-” who saw among 45 patients with auficuloventricular rhjmhm the
merging of P waves with QRS complexes in twenty-four instances.

Since it is known that the automaticit^*' of the specific fibers of the heart
diminishes gradually from above downward,® one would expect that the coronary
sinus area, in view of the high automaticity of the coronary sinus fibers, is always
next in line if the sinus node ceases to function and that this form of auriculo-

454

AMERICAN HEART JOURNAL

ventricular rhythm would occur more often. Actually, even in animal experi-
ments which are more susceptible to analysis, the destruction of the sinus node
is frequently followed by tliat form of auriculoventricular rhythm in which the
auricle and ventricle contract simultaneously and not bj' coronary sinus rhythm
as one might expect.

The fact that the coronary sinus area is in such close contact with nerve
fibers and ganglion cells, and is so easily influenced by exercise, carotid pressure,
and other factors, appears to us to offer the e.xplanation. Since the vagus nerve
exerts a greater chronotropic effect on the coronary sinus region than on the main
part of the auriculoventricular node,® it is clear that every factor which abol-
ishes the action of the sinus node by vagal effects, such as carotid sinus pres-
sure, digitalis, and refle.xes,“ may also lead to inhibition of the activity of the
coronary sinus. Under these circumstances, the pacemaker will be situated in
the deeper parts of the auriculoventricular node, and both auricle and ventricle
will be activated simultaneously. Moreover, even with stimulus formation in
the coronary sinus area, the reversed conduction to the auricle may be prevented
by a high vagal tonus so that electrocardiograms of these two forms would look
alike.

Blocking of the reversed conduction to the auricle is the most probable
reason why warming of the coronary sinus area in experiments on the Langen-
dorff heart caused a rapid auriculoventricular rhythm without causing the P
waves to become visible before the QRS complexes.®® In such experiments,
naturally normal conditions never prevail. It has been claimed that crushing
of the specific fibers of the sinus node, thus abolishing its activity by strong
stimuli, causes auriculoventricular rhythm with a positive P-R interval while
stopping the activity of the sinus node by cooling leads to auriculoventricular
rhythm in which auricle and ventricle contract simultaneously.^ These results
were not confirmed.®®

Some confusion was introduced into the picture when some authors®’^®’^®
called electrocardiograms with positive P waves in each lead and P-R intervals
of 0.12 second or less coronary sinus or coronary nodal rhythm. Such tracings,
however, belong to a normal sinus mechanism,®'' and the short P-R interval
must be attributed to other causes. It is -frequently found in thiamine de-
ficiency and is often seen in certain types of hypertension.®® A shortened P-R
interval with positive P waves and abnormal ventricular complexes is also seen
in the Wolff-Parkinson-White syndrome, which is explained by an abnormal
connection between auricle and ventricle.

The question arises as to whether or not one is justified in separating cor-
onary sinus rhythm from the rhythm originating in the auricuiar portion of the
auriculoventricular node. According to .some authorities, definite shortening of
the P-R interval would speak for upper auriculoventricular nodal rhythm while
a normal P-R interval would permit the diagnosis of coronary sinus rhythm.®®
Table I shows, however, that the length of the P-R interval during coronary
sinus rhythm will depend to a great degree on the length of the' P-R interval dur-
ing sinus rhythm in the respective patient. The P-R interv'^al during coronary

SCHERF AND HARRIS : CORONARY SINUS RHYTHM ;455

sinus rhythm is often, but not always, slightly shorter than during regular sinus
rhythm. With a P-R inter\'al of 0.18 second during regular sinus rhythm, a
P-R inter\*al of 0.12 second or more may be found during coronary sinus rhythm.
The condition of the auriculoventricular conduction system will influence the
P-R interval during both rhythms.

In experimental work on dogs, the P-R interval during coronary sinus
rhythm was shorter® or longer®” than during sinus rhythm. In the latter in-
stance, a very rapid heart rate usually prevailed which may explain the prolonga-
tion. In eight experiments on dogs, the length of the P-R interv^al during both
rhythms was compared®^ and was not found shorter when sinus rhythm changed
into coronary sinus rhythm. Here, however, the rate during coronarj’^ sinus
rhythm was also rapid. It appears, therefore, that until more is known about
this rhythm, the question of separation of the coronary sinus rhythm from the
“upper nodal rhythm” must be left open since the borderline between them is
still not sharply defined.

Since the term, coronary sinus rhythm, may easil}'' be confused with sinus
rhythm, the problem arises as to whether another designation for the rhythm
originating around the coronary sinus may not be preferable. Supranodal
rhythm, a term proposed for the auriculoventricular rhythm in which the P
wave precedes the QRS complex in a normal interv’-al,® may be considered as a
possible synonym.

While coronary sinus rhythm is usually found in an abnormal heart, par-
ticularly in patients with coronary sclerosis and hypertension, it may occur in
an otherwise apparently healthy person. A slight depression of the activity
of the sinus node and a moderate acceleration of the coronary sinus centers may
cause the abnormal rh 5 ^thm.

CONCLUSIONS

Electrocardiographic and clinical obseiA^ations made on thirty-one patients
with coronary'^ sinus rhythm are discussed.

Coronary sinus rhythm has a well-defined electrocardiographic picture with
a normal or slightly shortened P-R interval, low positive or absent P waves in
Lead I. and deep, inverted P waves, which are usually peaked, in Leads II and III.

A large majority of patients demonstrating this disturbance have evidence
of an organic heart lesion.

The anatomic and physiologic peculiarities of the specific tissue around the
orifice of the coronaiy?- sinus vein are discussed.

Differentiation between the rhythm originating in the area of the coronary
sinus and the rhythm originating in the upper part of the auriculoventricular node
is not yet possible.

450

AMERICAN HEART JOURNAL

REFERENCES

1. Aschoff, L.; Discussion, Deutsche nied. Wchnschr. 40: 1036, 1914.

2. Aschoff, L.: Die Herzstoerungen in ihrer Beziehung zum .spezifischen hluskelsystcm des

Herzens, Centralbl. f. allg. Path. ii. path Anat. 21: 433, 1910.

3 Borman, M. C., and Meek, W. J.: Coronary Sinus Rhythm, Arch. Int. Med. 47: 957,
1931.

4. Brandenburg, K., and Hoffman, P.; Wo entstehcn die normalen Bewegungsreize im Warm-

bluterherzen und welche Folgen fur die Schlagfolge hat ihre reiziose Ausschaltung?
Med. Klin. 8: 16, 1912.

5. Clerc., A., and Pezzi, L.: Le rhythme septal du coeur, .'\rch. dmal. du coeur. 13: 103, 1920.

6. Cohn, A. E., Kessel, L., and Mason, H. H.: Observations on the Functions of the Sino-

Auricular Node in the Dog, Heart 3: 311, 1911.

7. Danielopolu, D., and Proca, G. G.: Recherches sur le rhythme atrioventriculaire chez

I’homme, Arch, d.mal.du coeur 19; 247, 1926.

8. Eyster, j. A. E., and Meek, lY. J.: Studies on the Origin and Conduction of the Cardiac

Impulse, An. J. Ph 5 -siol. 61: 117, 1922.

9. Flaxman, N.: Atrioventricular Nodal Rhythm, Am. J. M. Sc. 201: 857, 1941.

10. Katz, L. N.: Electrocardiography, Philadelphia, 1941, Lea & Febiger.

11. Koch, W.; Ueber die Bedeutung der Reizbildungsstellen (kardiomotorischen Zentren) des

rechten Vorhofes beim Saugetierherzen, Arch. f. d. ges. Physiol. 151; 275, 1913.

12. Kung, S. K.; Herzblockstudien, Arch. f. exper. Path. u. Pharmakol. 153: 295, 1930.

13. Langendorf, R., Simon, A. J., and Katz, L. N.: A-V Block in A-V Nodal Rhythm, Am.

Heart J, 27; 209, 1944.

14. Lewis, T.; The Effect of Vagal Stimulation Upon Atrioventricular Rhythm, Heart 5: 247,

- 1913.

15. Lewis, T.; The Mechanism and Graphic Registration of the Heart Beat, ed. 3, London,

1925, Shaw & Sons.

16. Lewis T., and White, P. D.: The Effects of Premature Contractions in Vagotomised Dogs,

With Special Reference to Atrioventricular Rhythm, Heart 5: 335, 1914.

17. Meek, W. J., and Eyster, J. A. E.: Experiments on the Origin and Propagation of the

Impulse in the Heart, Heart 5: 227, 1914.

IS. Miller, R. A.: Auriculo- Ventricular Rhythm, Brit. Heart J. 6: 107, 1944.

19. Ruskin, A., and Decherd, G.; Momentary Atrial Electrical Axes, .^M. He.vrt J. 29: 633,

1945.

20. Ruskin, .A., McKinley, W. F., and Dechcrd, G. M.: Studies of the A-V Node: I\'. A

Clinical Study of Atrioventricular Nodal Rhythm, Texas Rep. Biol. & Med. 3: 86, 1945.

21. Schellong, F.: Ueber die elektrokardiographische Bestimmung des .Ausgang.spunktes von

V’orhofe.xtrasystolen, Miinchen. med. Wchnschr. 73: 614, 1926.

22. Scherf,D.: Experimental Sinoauricular Block, Proc.Soc. E.xper, Biol. & Med. 61: 286, 1946.

23. Scherf, D.: Ueber den atrioventricularen Rhythmus, Ztschr. f.d. ges. exper, Med. 78: 511,

1931.

24. Scherf, D.; Upper Auriculo- Ventricular Rhythm (Coronary Sinus Rhythm) Expcrimentalh-

Produced, Proc, Soc. Exper. Biol. & Med. 56: 220, 1944.

25. Scherf, D.: The Short P-R Interval and Its Occurrence in Hypertension, Bull. New York

M. Coll., Flower and Fifth Ave. Hosps. 4: 116, 1941.

26. Scherf, D., and Shookhoff, C.: Reizleitungsstorungen im Biindel, Wien. Arch.f.inn. Med.

10: 97, 1925.

27. Tawara, S.: Das Reizleitungssystem des Saugetierherzens, Jena, 1906, Gustav Fischer,

28. Wenckebach, K. F., and Winterberg, H.: Die unregelmassige Herztiitigkeit, Leipzig, 1927,

Wilhelm Engelniann.

29. Wilson, F. N.: Regular Ectopic Rhx'thnis, J. Lab. & Clin. Med. 1: 476, 1915.

30. Zahn, A.; Experimentelle Untersuchungen ueber Reizbildung und Reizloitung im Atri-

oventrikularknoten. Arch. f.d. ges. Physiol. 151: 247, 1913.

ABNORMALITIES OF THE RESPIRATORY PATTERN IN PATIENTS

WITH CARDIAC DYSPNEA

Howard E. Heyer, M.D.

Dallas, Texas

INTRODUCTION

D etailed analyses of the time relationships and variations in contour of
respiratory tracings recorded by the Marey pneumograph have not been
made in patients with cardiac dyspnea. Spirographic records of respiration in
patients with dyspnea due to heart disease hav’-e been concerned only with rate
and depth of breathing and not with variations in the relative duration of ex-
piration and inspiration or with changes in form. Furthermore, since spiro-
graphic tracings employ a slowlj^ moving cylinder, the records are closely com-
pressed so that variations in contour are not easily detected, and accurate meas-
urements of time relationships are difficult. By utilizing a rapidly moving drum,
the pneumograph yields tracings which can easily be measured. The present
study deals with an analysis of the time relationships of expiration and inspiration
and of changes in contour recorded by such means. Observations were made on
normal subjects as well as on patients with cardiac dyspnea and dyspnea due to
allergic bronchial asthma. The changes produced by exercise and by the admin-
istration of aminophylline were also noted.

METHOD OF STUDY

A record of the chest movements during breathing were made with a Marey pneumograph
which produced tracings on smoked paper on the rotating drum of a kymograph. Measurements
were made by means of a caliper micrometer of (a) the total duration of individual breaths, (b)
the duration of inspiration, and (c) the duration of e-xpiration. The estimated respiratory rate
for each breath was computed from the total duration of that cycle. Many breaths were thus
measured at various intervals on each record. The value for the respiratory rate, the durations
of inspiration and e-xpiration in each breath, plus the numerical ratio of duration of expiration
(in seconds): duration of inspiration (in seconds) were then expressed for each tracing. By this
method of study, observations were made on normal subjects, patients with dyspnea and pul-
monary congestion caused by heart failure, and patients with allergic bronchial asthma. Studies
of the vital capacity were also made before and after administration of aminophylline (theophylline
ethylenediamine) intravenously. The five normal subjects studied were medical students ranging
in age from 20 to 25 years. They were free of any clinical evidence of cardiac or pulmonary
disease; determinations of the circulation time (employing ether and decholin) and venous pres-
sure were made and were found to be normal. Eleven patients with heart disease, ranging in
age from 22 to 79 years, who were free of any history of allergic manifestations were studied
(sec Table I). 'I'hree of these patients suffered from syphilitic aortic insufficiency, four were diag-

From the Department of Internal Medicine, Southwestern Medical College, and the Medical Service
of Parkland Hospital.

Received for •publication Feb. 27, 194C.

4.57

458

AMERICAN HEART JOURNAL

nosed as having hypertensive heart disease and two as having arteriosclerotic heart disease, and
two rev'ealed evidence of mitral stenosis of rheumatic origin. All of these eleven subjects showed
clinical and roentgenologic evidence of pulmonary congestion, with moist r&les in the lung fields
and, in several cases, with a definite wheezing type of expiration. All tracings were taken in the
sitting position. The exercise in normal subjects consisted of forward bending from a standing
position, touching the toes with the fingers forty times. In the patients with heart disease, a few
were able to bend forward and touch the toes ten times, while in the remainder, swinging of the
arms across the chest from ten to sLxty times (depending on the capacity of the individual patient
for exercise) was sufficient to produce a definite hj’perpnea.

RESULTS

Normal Subjects at Rest . — In Fig. 1,A, is shown a typical tracing of a normal
subject at rest. The great majority of tracings revealed a similarity of contour
for each individual subject and the shape of the tracing tended to reproduce
itself in the same patient, with some minor deviations. The inspiratory down-
stroke was typically very slightly concave and the expiratory upstroke very
slightly convex (upward). The inspiratory phase tended to follow immediately
after expiration without pause. The infrequency of the expiratory pause
has been previously noted in an analysis of spirographic tracings by Caughey.'
The total duration of each individual breath varied inversely with the respiratory
rate, being shorter with a rapid rate and longer with a slow respiratory rate.
The numerical relationship of the duration of e.xpiration (in seconds) to the dura-
tion of inspiration (in seconds) varied, for the five subjects at rest, from 1.30:1
to 1.96:1 (Fig. 2). The average value for the expiratory: inspiratory ratio in the
five normal subjects at rest was 1.61. Otherwise stated, this means that the
average duration of expiration was 1.61 times as long as the average value for
inspiration in these normal subjects. This is in close agreement with values found
for this ratio by Mudd- by means of spirographic tracings.

Normal Subjects After Exercise . — Reference to Fig. ZA shows that after
exercise the respiratory rate increased sharply and the duration of inspiration
decreased somewhat, while the duration of expiration fell sharply. This de-
crease in the duration of expiration following e.xercise was of much greater
magnitude than the decrease in the duration of inspiration. Fig. ZB reveals
that the ratio, duration of expiration: duration of inspiration, also fell abruptly
in the cycles immediatel}'^ following exercise. After the subject recovered
from his hyperpnea the duration of inspiration, expiration, and the expiratory:
inspiratory ratio slowly returned toward resting values. The changes seen
in Figs. ZA and ZB were found to be a constant' pattern recurring after exercise
in all of the five normal subjects. Reference to Fig. 2 will show that the average
expiratory: inspiratory ratio for the group of normal subjects immediately after
exercise was found to be 1.39:1. It will be seen from these data that the typical
response to exercise in the normal subject was a selective shortening of the ex-
piratory' phase, and that it was mainly by shortening of this portion of each
breath that the increase in respiratory rate occurred. The ease with which this
change occurred indicated that there was, after exercise, both active participation
of the muscles of expiration and an absence of any expiratory obstruction.

HEYER: ABNORMALITIES OF RESPIRATORY PATTERN IN CARDIAC DYSPNEA 459

Patients With Heart Disease: Studies While Resting . — In Fig. 1, C and
is shown a definite lengthening of the expiratory phase in resting patients with
cardiac dyspnea; The tracings also were typified by an increase in upward con-
vexity of the expiratory limb. The relative duration of the expiratory phase was

C - Patient with severe cardiac asthma and
expiratory wheezing.

fvAAAAA/'^

D.- Patient with cardiac failure, pulmonary
congestion and expiratory wheeze.

E

Same patient as in D, immediately after
Theophylline with ethylene-diamine,

.5 gm. I .V .

Fig. 1 — Pneumographic tracing.s. Downstroke. inspiration; upstroke, e.xpiration.

found to be considerabb'' increased in all eleven patients with heart disease
studied,. Reference to Fig. 2 reveals that at rest the expiratory ;inspiratory
ratio gave definitely higher values than in the group of normal subjects. For
the entire group the average expiratory rinspiratory ratio was found to be 2.17 :1,
with a range extending from 1.52 to 2.90. In any given patient, although fluctua-

460

‘ AMERICAN' HEART JOURNAL

tions occurred, the values were always found to fall in this range. This prolonga-
tion of the expiratory phase, with upward convexity of the expiratory limb,
was most striking in the patients with frank cardiac asthma (Patients 1, 3, 4,
and 7, Table I, and Patient C, Fig. 1) but was also seen in the other patients with
heart disease who were free of the expiratory wheeze. These studies were inter-
preted as indicating that there is a definite relative prolongation of expiration
in the patient suffering from cardiac dyspnea.

. Fig, 2. — E.\plratory:inspiratory ratio in normal subjects and patients with heart disease. Middle
figure, mean for group: upper and lower figures, maximum and minimum range for group.

T.tBLK I. Expir.atory;Inspiratory R.atio of Patiests With Heart Disease

.WERAGE EXPIRATORY;INSPIR.\TORV
RATIO

PATIENT

; DIAGNOSIS !

i

1

1

! .AT REST

1

I

AFTER

EXERCISE

AFTER

AMINOPHYI-

I.INE

1 (J. H.)

Syphilitic aortic insufficiency; cardiac asthma

2.69

1 2.54

1.56

2 (C. M.)

Hypertensive heart disease

1.94

1 1.77 '

1.26

3 (C. W.)

Rheumatic heart disease; mitral stenosis:
cardiac asthma

2.03

i

i 2 18

1

1.60

4 (M. Y.)

Hypertensive heart disease; cardiac asthma .

2.38

2.00

5 (F. C.)

Syphilitic aortic insufficiency^

2.00

1.55

6 (G. S.t

Hypertensiy^e heart disease

2.03

2.00

! 1.50

7 (G. P.)

Hypertensive heart disease; cardiac asthma.

2.24

—

8 (J. J.)

Arteriosclerotic heart disease

2.07

9 (.M. G.)

.Arteriosclerotic heart disease

2. 12

1

1

10 (M. J.)

Rheumatic heart disease: mitral stenosis, . .

1.96

—

1

11 (W. L.)

Syphilitic aortic insufficiency'

2.30

—

—

Average expiratorxninspiratort- ratio

2.17

2.10

1

1.46

3A . — Actual duration of expiration and inspiration (in seconds) per breath in 7)ornial subject

(M. B.) at rest and after exercise.

FiR. 3B. — Expiratory; inspiratory ratio for individual breatlis of norraai su)»jcct (M. B.) at rest anti

after exorcise {same patient as in Fig. .3.4).

• COfllS

4G2

AMERICAN HEART JOURNAL

30

£5 ,

2

20 ■

«

a:

15 s

50 “

5

Pig. iA . — Actual duration of expiration and inspiration (in seconds) per breath in patient ^^1tI^
lieart disease at rest, after exercisoand after administration of aminophylline (Patient C. M.)

30

£5 ^

c
2

£0 1

15 t

10 '

5

Pig. 4B. — E.xpiratory. inspiratory ratio for indmdual breaths in patient with heart disease at rest, after
exercise, and after administration of aminophyliino (same patient as in P'ig. 4A).

heyer; abnormalities of respiratory pattern in cardiac dyspnea 463

Fatients With Cardiac Dyspnea: Studies After Exercise. — ^After an amount
of exercise tvhich \Yas capable of producing a perceptible hyperpnea in patients
with heart disease, the same type of observations were made. Reference to
Figs. AA and 4 jB reveals that, although there Avas an increase in respiratory^ rate
after exercise and a slight shortening of inspiration and expiration, this shortening
was proportionately the same for both phases of each respiratory cycle. The
selective shortening of expiration which was seen in normal subjects did not
occur in the patient with dyspnea, or occurred to a much less pronounced degree.
Careful observation of the patients with heart disease also revealed that after
exercise the accessory muscles of both expiration and inspiration were utilized
to a much greater degree than in normal subjects. Likewise, the expiratory:
inspiratory ratio remained at about the resting level, or decreased only slightly
in this group, as shown in Fig. 2. These findings were interpreted to indicate
that under ordinary conditions the cardiac patients were not capable of the selec-
tive shortening of the expiratory phase which was exhibited in normal subjects.

Patients With Asthma. — Two subjects with allergic bronchial asthma who
revealed prolonged wheezing expiration on ausculation were studied, and in each
case there was found to be a marked prolongation of the expiratory phase, with a
marked upward convexity of the expiratory limb (Fig. 1, j5). The average ex-
piratory :inspiratory ratio for these two patients at rest was found to be 2.14.
Since these subjects were presumed to have had active bronchospasm, this was
confirmatory proof of the presence of obstructive expiratory dyspnea. After
an amount of exercise (forward bending to touch toes) capable of producing
rharked dyspnea, the average expiratory :inspiratory ratio was found to be 1.81.
There was thus a slight shortening of the expiratory phase, but definitely not to
the same degree as in the normal subjects. After the administration of 0.5 Gm.
of aminophylline, intravenously, the expiratory^ :inspiratory ratio revealed an
average value for the two subjects of 1.67, and measurements revealed a definite
shortening of the expiratory phase. Furthermore, determinations of AUtal
capacity in the patients with asthma revealed abrupt increases of considerable
magnitude (Fig. 5) immediately after the drug. It was observed that expira-
tion occurred with much greater ease after this medication was administered.

Patients With Cardiac Dyspnea After Administration of Aminophylline . —
Figs. 4T and 45 reveal that after the administration of aminophylline there was
a marked relative shortening of the expiratory phase. Examination of the trac-
ings obtained during the administration of this drug also revealed a marked change
in contour (Fig. 1, D and E) with a sharp and rapid expiration. In the majority
of cases, the decrease in duration of expiration began within a few seconds after
the intravenous injection of the drug was started. Six patients with heart dis-
ease were given aminophylline. Five patients showed a selective shortening of
the expiratory phase with an average e.xpiratory: inspiratory ratio of 1.46 during
the intravenous administration of the drug. In comparison with the normal
group (Fig. 2) it will be noted that this approaches the value for the same ratio
determined after exercise in normal subjects. In each case there was a precipitous
rise in the respiratory rate after the drug, which was considered to be of central

■164

AMERICAN HEART JOURNAL

origin. This selective shortening of expiration which occurred after the ad-
ministration of aminophylline was the more remarkable in that acceleration of the
respiratory rate after exercise in patients with heart disease had failed to produce
such a relative shortening. The vital capacity was measured before and im-
mediately after the administration of aminophylline in five of the patients with
cardiac dyspnea. Reference to Fig. 5 reveals that whereas in a normal subject the
increase in vital capacity was insignificant, there was a definite increase in vital
capacity (ranging from 150 to 800 c.c.) in the patients with heart disease (Table
II). Since these increases occurred within periods of four to six minutes after

600

700

; 600

m

&

“ 500

a

^ 400

c

: 300

I 200

100

Rig. 5. — Increases in vital capacity after administration of aminopliylline, 0.5 Gm. intravenously, in
patients wth heart disease, patients with bronchial asthma, and in a normal subject.

• the beginning of the administration of the drug, and since moi&t rales were still
present on auscultation and x-ray films of the chest showed the persistence of pul-
monary congestion, the conclusion that there had been partial or complete
abolition of variable degrees of bronchospasm seemed warranted. This was
further supported by the fact that on auscultation of the chest of two of these
patients who suffered from cardiac asthma, there was a prompt disappearance of
expiratorj’^, Avheezing r&les during the injection. Reference to Fig. 2 reveals
that in the sixth subject, who suffered from very extreme pulmonary congestion,
there was no alteration in the duration of expiration and the expiratory rinspiratory
ratio after aminophylline. This ivas interpreted as indicating either that a
severe degree of bronchospasm which was not relieved by the drug was present
or that extreme pulmonary congestion had produced a leathery consistency of
the lung with loss of normal elastic contractility.

pulBOntry cengtttlon Subjfct

HEYER; ABNORMALITIES OF RESPIRATORY PATTERN IN CARDIAC DYSPNEA 465

Table II. Vital Capacities — Patiekts With Heart Disease

/

patient

!

1 AT REST

1 (c.c.)

predicted

NORMAL
(.%) .

1

AFTER

A^IINOPHYLLINE

(c.c.)

INCREASE

(c.c.) .

1

(J.H.)

2,200

48

2,700

500

2

(C. M.)

2,600

79

3,400

800

3

(M.S.)

2,200

50

2,650

450

'4

(C. W.)

1,900

43

2,350

450

5.

(M. G.)

2,100

49

2,250

150

DISCUSSION

The normal subjects were capable of a marked increase in respiratory rate
and depth after exercise without severe subjective symptoms of dyspnea. This
increase in rate was accomplished mainly by a selective shortening of the duration
of expiration. These changes occurred with ease, to meet the needs for in- .
creased ventilation, and there was no apparent obstruction in either inspiration
or expiration. Further, in a normal subject given aminophylline intravenously,
there was only an insignificant increase in vital capacity.

In patients with cardiac dyspnea, the striking factors noted were a relative
prolongation of the expiratory phase at rest, and a failure of this phase to undergo
relative shortening after exercise. This prolongation of the expiratory phase
was most strikingly seen in patients suffering from “cardiac” asthma, in whom
the expiratory distress was easily found on auscultation, as evidenced by a pro-
longed, wheezing type of expiration. The pneumographic tracings obtained in
both the patients with allergic asthma and those with cardiac asthma gave
patterns which were almost identical in appearance. In each case the expiratory
phase was markedly prolonged and was seen to possess an upward convexity.
Patients with allergic asthma have previously been shown to have a definite pro-
longation of the expiratory phase by measurement of spirographic tracings.-
Although the remaining seven cardiac patients with pulmonary congestion did
not show prolonged, wheezing expiration on physical examination, careful meas-
urements of their pneumographic tracings did reveal a relative prolongation of
the expiratory phase well above its relative duration as determined in the normal
subjects. The shape of the expiratory tracing in this latter group was inter-
mediate between the configurations obtained in the normal subject and those with
cardiac asthma but was also characterized by a tendency toward upward con-
vexity.

After the administration of aminophylline, there was a prompt shortening
of the relative duration of the expiratory phase in patients with cardiac dyspnea
and with allergic asthma. This was accompanied by a significant increase in the
vital capacity of both groups. Such increases in vital capacity in allergic asthma
after the administration of aminophylline were observed in 1937 by Greeiie,
Paul, and Feller,^ but data showing such increases do not appear to have been
presented for patients with cardiac dyspnea, despite the wide usage of amino-
phyllihe in this condition.

4(56

AMERICAN HEART JOURNAL

Although the prolonged, wheezing expiration of cardiac asthma has long
been recognized clinically, pneumographic tracings to confirm this prolongation
of expiration have been lacking. Since both the cardiac patients with asthma
and those without the asthniatic wheeze revealed a prolongation of the expiratory
phase, and since both groups revealed a prompt decrease in relative duration of
expiration after aminophylline, accompanied by a prompt rise in vital capacity,
the assumption that bronchospasm was present in both groups seems justified.
Since none of the patients with heart disease had any previous personal history
of allergic manifestations, it seemed unlikely that the expiratory difficulty
was due to allergy. The bronchospastic element observed probably has its origin
from reflexes arising in the congested pulmonarj' tissues. This aspect of the
problem needs further investigation.

SUMMARY

1. Pneumographic tracings of respiration revealed a similar type of dis-
tortion and prolongation of the expiratory phase in cardiac patients with pul-
monary congestion and in patients Avith allergic asthma. Expiration in these
patients did not undergo the relalh'^e shortening after exercise seen in normal
subjects.

2. During the administration of aminophylline intrax'^enously, the expira-
tory phase of the patients AAUth heart disease and asthma shortened promptly.
Determinations of Autal capacity in both groups also rcA^ealed abrupt increases
of considerable magnitude immediately after this drug.

3. The possibility that the changes obserx^ed in the patients with heart dis-
ease are due to reflex bronchospasm caused by pulmonary congestion is suggested.

The author Avishes to express his gratitude to Dr. Tinsley R. Harrison for his suggestions
and adv'ice throughout this study.

REFERENCES

1. Caughej', J. L., Jr.; Analysis of Breathing Pattern, Am. Rev. Tuberc. 48: 332, 1943.

2. Mudd. S. G.: Clinical SpirographAx I. Obserxmtions in Bronchial Asthma, Boston M.
&S.J. 193:345, 1925.

3. Greene, J. A., Paul, W. D., and Feller, A. E.: The Action of Theophylline With Ethylene-
diamine on Intrathecal and Venous Pressures in Cardiac Failure and on Bronchial Obstruc-
tion in Cardiac Failure and in Bronchial Asthma, J. A. M. A. 109: 1712, 1937.

4. Silverman, L., Lee. R. C., and Drinker, C. K.: A New Method for Studying Breathing,
with Observations Upon Normal and Abnormal Subjects, J. Clin. Investigation 23: 907, 1944.

5. Schmidt, C. F., and Harer, W. B.: The Action of Drugs on Respiration. I. The Mor-
phine Series, J. Exper. Med. 37: 47, 1923.

6. Gesell, R., and White, F.; Recruitment of Muscular Activity and the Central Neurone
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7. Weiss, S., and Robb, G. P.: Cardiac Asthma (Paroxysmal Cardiac Dvspnea) and the
Syndrome of Left Ventricular Failure, J. A. M. A. 100: 1841, 1933.

8. \’'aughan, W. T., Perkins, R. M., and Derbes, V. J.; Epinephrine and Ephedrine Analogues

. and Their Clinical Assay. J. Lab. & Clin. Med. 28: 255, 1942.

9. .Adrian, E. D.; .MTerent Impulses in the Vagus and Their Effect on Respiration, J. Physiol.
(9: 332, 1933.

10. Peabody, F. W., and Wentworth, J. A.; Clinical Studies of the Respiration. IV. The
Vital Capacity of the Lungs and Its Relation to Dyspnea, Arch. Int. Med. 20: 443, 1917.

HEYER; ABNORMALITIES OF RESPIRATORY PATTERN IN CARDIAC DYSPNEA 467

n. Binger, C. A. L.: The Lung Volume in Heart Disease, J. Exper. Med. 38: 445, 1923.

12. Harrison, T. R., Calhoun, J. A., and Harrison, W. G., Jr.: Congestive Heart Failure.

XXI. Observations Concerning the Mechanism of Cardiac Asthma, Arch. Int. Med. 5.3;
911, 1934.' >

13. Steffensen, E. H., Brookhart, J. M., and Gesell, R.: Proprioceptive Respiratory Refle.\e.s
of the Vagus Nerv'e, Am. J. Phj'siol. 119: 517, 1937.

14. Gesell, R., Steffensen, E. H., and Brookhart, J. M.: The Interaction of the Rate and Depth
' Components of Respiratory Control, Am. J. Phj'siol. 120: 105, 1937.

15. Adrian, E. D., and Bronk, D. W.: The Discharge of Impulses in Motor Nerve Fibers.
I. Impulses in Single Fibers of the Phrenic Nervm, J. Physiol. 66; 81, 1928.

16. Cournand, A., Brock, H. J., Rappaport, I., and Richards, D. W.: Disturbance of Action of
Respiratory Muscles As a Contributing Cause of Dyspnea, .4rch. Int. Med. .57: 1008, 1936.

17. Burwell, S. C.: The Pathological Physiology of Early Manifestations of Left Ventricular
Failure, Ann. Int. Med. 16: 105, 1942,

18. Herrmann, G., Agnesworth, M. B., and Martin, J.: Successful Treatment of Persistent ,
Extreme Dyspnea "Status Asthmaticus” — Use of Theophylline Ethylenediamine (Amino,
phylline. U. S. P.) Intravenously, J. Lab. & Clin. Med. 23; 135, 1937.

THE INFLUENCE OF AGE ON BLOOD PRESSURE

A Study of 5,331 White Male Subjects

HiuVry I. Russek, M.D., and Maurice M. Rath, Fh.D., M.D., Staten Island,
N. Y., Burton L. Zoiiman, M.D., Brooklyn, N. Y., and
Isidore Miller, M.D., New York, N. Y.

T he question as to whether or not a physiologic rise in normal blood pressure
occurs with advancing age has not thus far been satisfactorily answered.
Conflicting clinical and statistical interpretations moreover have led to a wide
divergence of authoritative opinion as to what constitutes the upper limit of
normal at different ages.

Within recent years the highest acceptable level of the systolic reading has
been persistentlj'^ lowered so that ‘TOO plus the age” no longer finds favor even
with those who employ the most liberal critera for this physiologic measurement.
In the last fifteen years many authorities*'® have designated 140 mm. Hg as
the ceiling level for normal-systolic blood pressure irrespective of age. According
to this view,® a systolic reading above 140 mm. ‘‘is just as abnormal in an old
man as in a young one.” On the other hand, it has been shown repeatedly that
a relatively high percentage of normal persons in middle life and old age manifest
levels in excess of this limit.®'® Indeed, one of us (H. 1. R.)® found that 64 per
cent of a group of one thousand elderly seamen would have been considered to
have abnormally high blood pressure by this delimitation. Furthermore, if the
upper level of normal systolic blood pressure had been lowered to 120 mm. Hg,
as advocated by Robinson and Brucer,® only 13 per cent of this'entire series would
have qualified as normal. In distinct contrast with these findings in older male
groups have been the obsen'-ations of blood pressure levels in young male adults.
Thus, various reports*®'*® indicate that only 1 to 3 per cent of Army examinees
in World War II had systolic blood pressures in excess of 150.

White*® has stated that under the excitement of the examination, 160 mm.
might be acceptable as the upper limit of the systolic blood pressure, but he
would not raise the diastolic level much, if any, above 90 millimeters. Never-
theless, a recent publication by White and associates'^ suggests that even transient
elevation of the systolic blood pressure above 150 is significant as a forerunner of
sustained hypertension. The same conclusion was reached in regard to diastolic
levels above 90. The follow-up studies of Hines,*® however, are not in accord with
this view. This author noted that ‘‘in the group of patients who had systolic
blood pre ssure of more than 140 mm. but diastolic blood pressure of less than

From tlic Cardlo-vascular Research Division. U S. Marine Hospital, Staten Island, N, Y.
"Published ■»\ith permission of the Surgeon Generai, U S Public Health Service,

Receiveti for publication Dec 2(1, 1045.

46S

RUSSEK ET AL. ; INFLUENCE OF AGE ON BLOOD PRESSURE 469

85 mm., none had subsequent hypertension.” It appeared to Hines that a dias-
tolic reading of 85 mm. represents a critical level with respect to future hyper-
tensive disease. The prognostic significance of transient elevation of the systolic
blood pressure, therefore, does not yet seem clearly established.

In an endeavor to investigate further the relationship between age and
blood pressure, we have studied an unselected group of merchant seamen, coast-
guardsmen, and civilian male subjects.

.MATERIAL FOR STUDY

The blood pressure levels of 5331 white men between the ages of 40 and
95 years were analyzed. These subjects were observed at the U. S. Marine
Hospital, Staten Island, the U. S. Public Health Service Dispensary, Washington,
D. C., Sailors Snug Harbor, Staten Island, and the New York City Farm Colony,
Staten Island. The latter two institutions were the source of most of the aged
individuals. The subjects from the Marine Hospital were healthy merchant
seamen and coastguardsmen chiefly in the fifth and sixth decades of life. The
subjects from Sailors Snug Harbor were older, retired seamen in the seventh to
tenth decades of life. An analysis of this group was previously reported by
one of us (H.I. R.).® The subjects from the U. S. Public Health Service Dispen-
sary were candidates for civil service appointments, while those from the New
York City Farm Colony were an older group of civilians, unemployed, indigent, or
incapacitated by the infirmities of senescence. A stud}' of the latter group has
also been reported by one of us (I. M.)® In all instances, two or more blood pres-
sure readings were taken. In the younger subjects an attempt was made to
minimize the effect of excitement by instituting a short period of rest between
blood pressure readings and a friendly chat. The older subjects were accus-
tomed to having their blood pressure measured during routine morning rounds.
All of the subjects were ambulatory. The persons observed at the various
institutions numbered as follows:

U. S. Marine Ho.spital 1 ,588

Sailors Snug Harbor 1,000

U. S. Public Health Service Dispensary 1 ,887
New York City Farm Colony 856

Total 5,3.H

RESULTS

Table I represents an analysis of average systolic and average diastolic blood
pressure* by five- and ten-year intervals. It is observed that average systolic
blood pressure and pulse pressure rise with advancing years. Average diastolic

*Thc level at the Beginning of the fourth phase was taken as the diastolic blood

prfs-sure.

-170

AMERICAN HEART JOURNAL

'I'.vBLE I. Average Systolic and Diastolic Blood Pressure of Male
Subjects 40 to 95 Years of Age

\GE

(\R.)

, NUMBER

, Of

CASES

t

1

j AVER.\GE

' SYSTOLIC BLOOD
[ PRESSURE

j (mm. hg)

I

T

*

AVERrVGE
DIASTOLIC BLOOD
PRESSURE

(mm. kg')

T

AVERrVGE

PULSE

PRESSURE

(mm. hg)

40

to

44

1

i 831

1

1 133

.3

±

0

.57t

1

84.8

4 -

0

.37

48.5

45

to

49

j 809

; 137.

.0

+

0

.68

4,

.0

1 86.6

+

0.

,36

1

.0

50.4

50

to

54

767

138

9

0.

.82

1.

.8

[ 87.0

±

0.

.42

0

.6

51.9

55

to

59

• 647

142,

4

±

1.

.02

2.

.6

87.7

±

0.

.57

1

.0

54. 7

60

to

64

1 566 1

147.

7

4 -

1.

,16

3.

.4

87.6

±

0.

60

0

.0

60.1

65

to

69

558 '

154,

2

_U

1 .

,22

4

1

88.5

4 .

0.

67

0,

.9

65.7

70

to

74

I 402 i

155.

1

±

1.

37

1.

6

87.0

+

0

72

I.

.4

68.1

75

to

79

i 370

t 160.

6

±

1.

,31

2_

6

88.2

+

0.

88

1.

1

72.4

80

to

84

! 255

160.

4

4 -

1.

,65

6.

0

86.8

+

0.

95

1 1-

.1

73.6

85

to

95 1

[ 126

164.

0

+

2,

22

1.

5

90.0

±

1 .

26

1 .

,5

74.0

40

to

49

1,640

135.

1

+

0.

44

i

85.8

+

0

27

49.3

50

to

59 !

1,414

140.

,8

±

0.

,64

7.

4

87.4

+

0.

35

3.

,7

53.4

60

to

69

1,124

150.

,8

+

0

84

9.

.5

88 1

4 -

0

50

1 .

.2

62.7

70

to

79 i

772

158.

6

+

0.

96

6.

1

87.6

4 -

0

57

0.

5

71.0

80

to

95

381

161.

7

±

1 .

34

1.

8

87.9

+

0.

78

0.

.5

73.8

40

to

59 i

3,054

138.

5

+

0.

37

86.5

0.

21

52.0

60

to

95

2,277

1 153.

1

9

+

0.

58

23.

0

87.8

+

0.

32

3.

2

66.1

40

to

95

j

5,331

144.

7

±

0.

35

1

87.1

+

0 .

18

57.6

*T. employed in this and Tables II, III, and IV, represents the number of times greater the observetl
dllloroncc between an average or proportion of one age group and that of the preceding age group is
t ban the standard error of that diflercnce.
tThesc values arc standard errors.

blood pressure, on the other hand, increases onlj'^ slightly with age, the largest
increment occurring between the fifth and sixth decades. These trends are
shown in Figs. 1 and 2.

*

Table II was constructed by calculating the percentage of persons in each
age group having “normal” blood pressure (149/195 or less) , systolic hypertension
(systolic, 150 mm. or over; diastolic, 95 mm. or less), and diastolic hypertension
(diastolic, 96 mm. or over). A steady and progressive decrease in the incidence
of “normal” blood pressure occurs with advance of age, the fall being from 87.2
per cent in the 40- to 44-year age group to 27.8 per cent in the 85- to 95-year

group. In direct contrast, a marked increase is noted in the frequenej'^ of
systolic hypertension, the change being from 4.2 per cent to 45.2 per cent in the
same age interval, ^^'hen diastolic hypertension is analyzed, the incidence is
found to rise from 9.6 per cent in the fifth decade to 20.2 per cent in the seventh
decade, remaining relatively unchanged thereafter. Fig. 3 graphically represents
the variations with age in the incidence of “normal” blood pressure, systolic
hypertension, and diastolic hypertension.

RUSSEK ET AE. : INFLUENCE OF AGE ON BLOOD PRESSURE

DIASTOLIC HYPERTEHSIVES

SYSTOLIC RTPERTSJJSim

ALL CROUPS COKBIHZD

IIORHAL CROUP

Fig, 1. — The relationship of age to average systolic l)loo(I pressure.

DIASTOLIC HYPERTEHSIVES

ALL GROUPS COKBIHED

SYSTOLIC HYPEHTSK3IVE3

KORHAL CROUP

The relaiionship of age to average diastolic l)loocl pressun

sovsKsoHaa

472

AMERICAN HEART JOURNAL

I'Mg. 3. — Tlip relationsliip of age to percentage incidence of normal blood pressure (A), diastolic hyper-
tension (J3), and systolic hypertension (C).

Table II. Percentage Incidence of Normal Blood Pressure, Systolic Hypertension,

AND Diastolic Hypertension

age

(YR.)

normal blood

PRESSURE

SYSTOLIC

HYPERTENSION

DIASTOLIC

HYPERTENSION

%

T

%

T

%

T

40 to 44

87.2

4.2

8.5

45 to 49

81.7

3.1

7.5

2.9

10.8

1.5

50 to 54

74.8

3.3

11.5

2.6

13.7

1.8

55 to 59

68.2

2.7

14.7

1.8

17.1

1.8

60 to 64

57.9

3,7

22.8

3.6

19.3 1

0.9

65 to 69

47.8

3.4

31.0

3.1

1 21.1

0.8

70 to 74

43.0

1.4

38.3

2.3

18.7

1.0

75 to 79

35.1

2.2

43.0

1.3

21.9

1.1

80 to 84

36.1

0.2

44.3

0.1

19.6

0.8

■ 85 to 95

! 27.8

1.6

45.2

0.1

27.0

1.6

40 to 49

84.5

5.8

9.6

50 to 59

71.8

8.4

12.9

6.7

15.3

4.7

60 to 69

52.9

9.9

26.9

8.7

20.2

3.2

70 to 79

39.2

6.0

40.5

6.1

20.2

0.0

80 to 95

33.3

2.0

44 6

3.6

22.0

0.7

40 to 59

78.6

9.1

12.3

60 (0 95

45.0

18.6

34.4

10.5

20.6

3.2

40 to Q5

64 3

20.0

15.8

RUSSEK ET AL. : INFLUENCE OF AGE ON BLOOD PRESSURE 473

Tabi.e III. “Normal” Blood Pressure Group

AGE

(YR.)

number

OF

CASES

SYSTOLIC BLOOD PRESSURE

DIASTOLIC BLOOD PRESSURE

PULSE

PRESSURE

AVERAGE

(MM.)

!

AVERAGE :

(-MM.)

T

average

(mm.)

in

40 to 49

i 1,386

129.6 ± 0.28

! 80.9 ± 0.20 ;

48.7 .

50 to 59

! 1,015

129.6 ± 0.38

0.0

2.5

49.5

60 to 69

595

130.2 ± 0.55

i 0.9

7.4

53.4

70 to 79

30.3

133.7 ± 0.87

3.4

75.7 ± 0.60

1.5

58.0

80 to 95

127

134.1 ± 1.0 1

0.3

74.5 ± 0.93

1.0

59.6

40 to 59

2,401 1

80.6 ± 0.16

49.0

60 to 95

1,025 j

131.7 ± 0.40

4.5

; 76.2 ± 0.30

13.3

55.5

40 to 95

3,426

1

79.2 ± 0.15

1

j

i

1 51.1

AGE

(YR.)

SYSTOLIC BLOOD
PRESSURE

1

DIASTOLIC BLOOD PRESSURE |

120/80 OR LESS

140-149 MM.

90-95 MM.

BELOW

70 .MM.

%

T

1

%

■nH

%

T

%

1 ^

40 to 49

18.6

i

i 15.4

1

3.6

27.5

1

SO to 59

24.4

1 2.0

14.4

i 0.7

6.4

3.0

29.0

0.8

60 to 69 i

28.2

i 3.0

12.2

1 1.3

15.1

5.2

32. 1

! 1.3

70 to 79 !

36.3

2.4

15.1

j 1.5

20.1

1.7 i

26.0

1.9

80 to 95

40.9

0.9

15.7

0.2

1 21.2

0.3

1

26.7

1 0.0

40 to 59

19.8

15.0

1 4.7

28. 1

60 to 95

32.1

7.2

13.5

1.1

j 16.5

9.5

29.7

1.1

40 to 95

23.5

!

!

14.6

1

1 8.5

1 1

I 1

! j

28.6

The trends of "normal” systolic and "normal” diastolic blood pressure are
analyzed with respect to age in Table III. Average "normal” systolic pressure
tends to increase progressively from 129.6 mm. in the 40- to 49-year age group
to 134.1 mm. in the 80- to 95-year age group. Comparison of average "normal”
systolic pressure in the age period 40 to 59 with that in the age period 60 to 95
shows a significantly higher level in the older group. Average "normal” diastolic
pressure tends to decrease progressively from 80.9 mm. in the 40- to 49-year ,
age group to 74.5 mm. in the 80- to'95-year age group. The incidence of blood
pressures of 120/80 or less shows no significant change with advancing years.
In sharp contrast, one observes a significant rise with age in the frequency of
systolic blood pressures between 140 and 149 millimeters. There is also an in-
creasing incidence of diastolic blood pressures below 70. The frequency of
diastolic pressures over 90 mm., on the other hand, is not altered in the “normal”
group with succeeding decades. It appears, therefore, that the trend of normal
systolic blood pressure with age is upward, while that of normal diastolic blood
pressure is downward. If the rise in "normal” systolic pressure were due solely

TAriLK IV. Average

■m

AMERICAN HEART JOURNAL

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RUSSEKETAL. : INFLUE^•CE OF AGE ON BLOOD PRESSURE 475

to potential hypertension in the “normal” group, an associated rise in “normal”
diastolic pressure should be demonstrable. This, however, is not found. On
the contrary, average “normal” diastolic pressure actually falls with age and
-there is, correspondingly, a progressive increase in the percentage of subjects
with low levels of normal.

Our studies indicate that the average systolic blood pressure of each of the
groups, “normal,” systolic hypertensive, and diastolic hypertensive, increases
significantly with advance of age. With, respect to diastolic blood pressure,
the averages for both “normals” and subjects with systolic hypertension decrease
with age, while the average diastolic blood pressure for subjects with diastolic
hypertension remains unchanged (Tables III and IV). Since in none of these in-
dividual blood pressure groups does the average diastolic pressure rise w'ith age,
the question may be raised as to why it shows this tendency when the entire
group is considered as a whole. The answer undoubtedly lies in the rising in-
cidence of diastolic hypertension with advancing age, a factor tending to elevate
the average pressure of the combined groups. The trends in average systolic and
average diastolic blood pressure for each of the blood pressure groups as well as
for the total series is shown in Figs. 1 and 2, respectively.

DISCUSSION

Increase in average blood pressure with age does not constitute proof of a
physiologic rise in normal blood pressure, for it is obvious that the hypertensive
levels in the total population may distort the true picture of normal blood pressure
trends. Robinson and Brucer, using 140/90 as the upper limit of normal, re-
ported no increase in the mean arterial blood pressure with advancing years and
thus concluded that normal blood pressure remains constant throughout life.
Our examination of their data, however, does not uphold this view, for we dis-
covered a significant rise with age in the a’ncidence of systolic blood pressures
in their upper range of “normal” (130 to 139 mm.). Furthermore, although the.se
authors contended that the conclusions from their analysis would have been the
same if the level of delimitation had been placed at 150 s^'stolic and 95 diastolic,
we have found, employing these ceiling values for normal in our series, that there
is a tendency for normal systolic blood pressure to rise with advance of age
(Table III). Moreover, if this increase were due chiefly to the presence of poten-
tial or latent hypertension in the “normal” group as alleged by these authors,
a concomitant rise in diastolic blood pressure would also have been evident;
Actually, however, a decrease rather than increase in “normal” diastolic pressure
is observed with advance of age. We noted that the frequency of upper levels
of “normal” diastolic blood pressure (90 to 95 mm.) remains unchanged when
successively older groups are analyzed. On the other hand, the percentage of
persons with systolic pressures in the upper range of “normal” (140 to 149 mm.),
as well as the percentage with diastolic pressures in the lower range of normal
(below 70. mm.), increase appreciably. Robinson and Brucer similarly found a
rising incidence of low diastolic levels after the age of 55 years but admitted

47G

AMERICAN HEART JOURNAL

that they “have not adequately accounted for this variation.” The findings
strongly suggest, therefore, that age exerts a definite influence on normal blood
pressure, the systolic level rising and the diastolic level falling with advancing
years. Why normal blood pressure is affected in this manner will now be con-
sidered.

Observations of various workers indicate that the physiologic process of
aging influences all blood pressure levels through two maj'or mechanisms, one
neurogenic the other vascular. Russek’® and Russek and Zohman,'" using the
cold-pressor test, have demonstrated that the reactibility of the blood pressure
increases progressively as persons grow older. This increase in vasopressor
response is attributed by Raab’* to “increasing irritability of the cerebromedul-
lary vasoconstrictor centers” with advancing years. The latter allegedly results
from ischemia of the nerve centers controlling vascular tonus, a consequence of
diminution in cerebral blood flow due to arteriolar sclerotic changes. That
hj'pertension may actually arise from decreased cerebral blood flow is suggested
by the recent experiments of Fishback and co-workers,*® who were able to produce
sustained elevation of the blood pressure in animals by ligating the arteries sup-
plying the head. On the other hand, Dock®® rejects the e.xplanation that cerebral
arteriosclerosis is responsible for increased vasomotor irritability and hyperten-
sion, declaring that these are rather the result of deterioration of the central
nervous system with trophic loss of neurones associated with aging. Thus,
vascular hyperreactibility and benign hypertension, in the opinion of Dock, are
similar in origin to “senile intention tremor. Parkinsonism, and other involutional
disorders of specific neurone groups.” Whatever the explanation, evidence
suggests that s 5 '^stolic and diastolic blood pressures are increasingly prone to
transient elevation with advancing years. Although it has been main-
tained that a hyperreactive vascular system portends future hypertension,
Russek and Zohman*' found an increasing frequency of hyperreaction with age in
subjects “unlikel}’’ to develop the disease” and even in those with hypotension.
It seems possible, therefore, that other factors in addition to neurogenic vascular
hyperreactibility are essential for the development of sustained hypertension.
Sensitization of the vascular system by hormones from the adrenal corte.x,
adrenalin, angiotonin, or other substances, may be a necessary accompaniment.
That a neurogenic mechanism is of importance in the pathogenesis of hyperten-
sion is reflected in the ability of caudal anesthesia®*’®® and lumbodorsal splan-
chnicectom}’^®® to reduce hypertensive levels to normal in many cases. The
neurogenic factor, therefore, appears to exert an influence tending to augment
both systolic and diastolic blood pressure with advance of age.

A second mechanism, of purely vascular origin, also alters the blood pressure
as one grows older. Diminution in the elasticity of the aorta and its large
branches due to arteriosclerosis has been held responsible for the appearance
of systolic hypertension in older groups. However, Herringham and Wills®*
and others have shown that the elasticity of arteries diminishes progressive!}'’
with advancing years, becoming particularly marked with the fifth decade.
Although loss of elasticity is frequently accepted as synonymous with ather-

RUSSEK ETAL. ; INFLUENCE OE AGE ON BLOOD PRESSURE 477

osclerosis, it has been emphasized that many elderly persons have vessels with
little eleasticity remaining but no atherosclerosis. Contrariwise, extensive scler-
otic changes may be present even in young persons .without significant loss of
elasticity.^® Normal vascular aging, therefore, appears to be reflected in a rising
systolic pressure and falling diastolic pressure with advancing years. Systolic
hypertension in the aged is undoubtedly a manifestation of the same vascular
process. Considered in this light, these changes, may be compared to the physi-
ologic alterations occurring in the hair, skin, skeleton, and other structures with
advancing years.

These considerations make it apparent that the neurogenic and vascular
factors are summated in their influence upon systolic blood pressure while exert-
ing opposing influences upon diastolic blood pressure. In normal persons
> and in those with systolic hypertension the vascular factor appears to dominate,
as shown by a tendency of the average diastolic blood pressure to fall with age
in each of the two groups. This change, hoAvever, is not observed in the group
with diastolic hypertension.

Although only 9.1 per cent of the persons between 40 and 59 years had
systolic hypertension, 34.4 per cent of the persons between 60 and 95 years
manifested this type of blood pressure elevation. If it be accepted, therefore,
that systolic blood pressure increases with age and that systolic hypertension
is a normal finding in later life, the upper limit of normal systolic pressure for
older groups must be elevated considerably above present-day standards. In-
deed, the old dictum “100 plus the age’’ may yet regain its former prestige
as an index of normal systolic blood pressure.

Acceptance of 140 mm. as the ceiling level for normal systolic blood pressure
as advocated by others would have eliminated almost one-half (49.3 per cent)
of our entire series. For the subjects between the ages of 60 and 95 years, 69.1
per cent would have been excluded by this limit. Furthermore, only 18.3
per cent of the entire series would have qualified as normal under the standards
set by Robinson and Brucer (120/80 or less). Although 69.1 per cent of the
persons between 60 and 95 years had systolic pressures of 140 mm. and over,
only 41.9 per cent had diastolic pressures of 90 mm. and over. Hence, if these
readings are employed as limits of normal, it is evident that there is a wide dis-
parity in the “screening’’ value of the respective levels.

Most authorities accept small increments in the diastolic blood pressure
with age as physiologic. We have pointed out, however, the tendency of normal
diastolic blood pressure to fall rather than rise with age. It seems likely from
studies of younger groups that normal diastolic blood pressure rarely exceeds
90.13-15 If is established, our observations would indicate that an even
lower ceiling may be applicable to older age groups.

From these considerations it would appear that essential hypertension
cannot be defined solely in terms of the systolic blood pressure, although this
has been a common practice in earlier literature and even in some current litera-
ture. In general, our observations seem to support the views of Hines,^® who,
in his follow-up studies, noted that the diastolic pressure alone and not the systolic
is of value in prognosticating the subsequent development of hypertension.

478

AilERICAN HEART JOURNAL

SUMMARY AND CONCLUSIONS

Although previous studies of unselected groups have demonstrated a
progressive rise in average -systolic and diastolic blood pressure with advancing
years, no convincing proof has been offered that normal blood pressure increases
physiologically with respect to age. Considerable difference of opinion exists,
therefore, as to what constitutes the limits of normal at various periods of life.

A statistical analysis of the blood pressure levels of 5,331 white male subj’ects
between the ages of 40 and 95 years is presented. The variations in blood pres-
sure with age and the inferences drawn therefrom are as follows:

1. Average systolic blood pressure increases significantly with age, whereas
average diastolic blood pressure shows little variation after the sixth decade.

2. The incidence of “normal” blood pressure (149/95 or less) falls markedly
with age so that less than one-half (45.0 per cent) of the subjects 60 years old
and older belong to this group.

3. The frequency of systolic hypertension rises sharply with advancing
years. Approximately one-third (34.4 per cent) of the subjects 60 years of age
and over show this type of blood pressure elevation.

4. The incidence of diastolic hypertension increases significantly up to
the seventh decade, remaining relatively unchanged thereafter.

5. Normal systolic blood pressure tends to increase with age. The fre-
quency of upper levels of “normal” (140 to 149 mm.) rises appreciably with ad-
vancing years.

6. The assumption that normal diastolic blood pressure increases with
age is unfounded. Actually, a progressive decrease occurs with succeeding dec-
ades with the result that there is an increasing frequency of low diastolic levels
(below 70 mm.) with advancing years.

7. The rise in normal systolic pressure and concomitant fall in normal
diastolic pressure are primarily the result of progressive diminution in the elas-
ticity of the aorta and its large branches associated Avith the process of aging
(vascular factor).

8. The same physiologic mechanism is responsible for the increasing in-
cidence of systolic hypertension AA'^hich is merely the hemodynamic reflection
of vascular aging.

9. Physiologic changes in the central nervous system leading to vascular
hyperreactibility A\dth advancing years similarly e.xert an important influence
upon the blood pressure trends of all groups (neurogenic factor).

10. Both mechanisms (vascular and neurogenic) are summated in their
effect upon systolic blood pressure AA-^hile exerting opposing influences upon
diastolic blood pressure.

11. The old maxim “100 plus the age” may actually be a fair index of
normal systolic blood pressure.

12. Although the ceiling for normal diastolic blood pressure has been
set at 90 mm. Hg, an even low’^er level appears applicable after middle age.

13. Essential hypertension cannot be defined solely in terms of the systolic
blood pressure. It is the diastolic IcA'el alone that determines the existence
of this disease.

RUSSEK ET AL. : INFLUENCE OF AGE ON BLOOD PRESSURE

479

REFERENCES

1. Stieglitz, E. J.: i.4bnormal Arterial Tension, New York, 1935, National Medical Book

; Company.

2. Allen, E. V., in Musser, J. H.; Internal Medicine, ed. 3, Philadelphia, 1938, Lea & Febiger.

3. Alvarez, W. C., and Stanley, L. I.; Blood Pressure in Six Thousand Prisoners and Four

Hundred Prison Guards; Statistical Analysis, Arch. Int. Med. 46: 17, 1930.

4. Huber, E. G.; Svstolic and Diastolic Blood Pressure in Healthy Men, Human Biol. 5:

542, 1933.

5. Faught, F. A.: Simple Method for Determining Normal Average Systolic Blood Pressure

at Any Age, M. J. & Rec. 135: 160, 1932.

6. Miller, I.: Blood Pressure Studies in the Aged, New York State J. Med. 41: 1631, 1941.

7. Master, A. M., Marks, H. H., and Dack, S.: Hypertension in People Over Fortv, J. A. M. A.

121: 1251, 1943.

8. Russek, H. I.: Blood Pressure in the Aged, Am. He.\rt J. 26: 11, 1943.

9. Robinson, S. C., and Brucer, M.: Range of Normal Blood Pressure; Statistical and Clinical

Study of 11,383 Persons, Arch. Int. Med. 64: 409, 1939.

10. Folk, O. H., McGill, K. H., and Rowntree, L. G.t Analysis of Reports of Physical

Examinations, M. Statist. Bull., Sel. Ser\\ Syst., No. 1, Nov. 10, 1941, Washington,
D. C., National Headquarters, Selective Service System.

11. (a) Wilburne, M., and Ceccolini, E. M.; A Note on the Incidence of Arterial Hyperten-

sion in 25,000 Army Examinees, Army M. Bull. 68: 118, 1943.

(b) Wilburne, M., and Ceccolini, E. M.: Heart Disease in Selective Serxdce Examinees;
Study of 20,000 Examinees in Pacihc Northwest, Am. J. M. Sc. 207: 204, 1944.

12. Flaxman, N.: Initial Cardiac Examination of 23,000 Inductees and Volunteers, .^m. J.

M. Sc. 209: 657, 1945.

13. White, P. D.: Cardiac Problems in War Time, Ann. Int. Med. 18: 323, 1943.

14. Levy, R. L,, White, P. D., Sttoud, W. S., and Hillman, C. C.: Transient Hypertension,

the Relative Prognostic Importance of Various Systolic and Diastolic Levels, J, A.
M. A. 128: 1059, 1945.

15. Hines, E. A., Jr.: Range of Normal Blood Pressure and Subsequent Development of Hyper-

tension; Follow-up Study of 1,522 Patients, J. A. M. A. 115: 271, 1940.

16. Russek, H. L: The Significance of Vascular Hyperreaction as Measured by the Cold-

Pressor Test, Am. Heart J. 26: 398, 1943.

17. Russek, H. L, and Zohman, B. L.: Influence of Age Upon Blood Pressure Response to the

Cold-Pressor Test, Am. He.art J. 29: 113, 1945.

18. Raab, W.: Hormonal, Central and Renal Origin of “Essential” Hypetrension (Cerebral

and Renal Arteriosclerotic Ischemia as Causal Factors), Ann. Int. Med. 14: 1981,
1941.

19. Fishback, H. R., Dutra, F. E., and MacCamy, E. T.: The Production of Chronic Hyper-

tension in Dogs bv Progressive Ligation of Arteries Supplying the Head, J. Lab. &
Clin. Med. 28; 1187, 1943.

20. Dock, W.; Presbycardia, or Aging of the Myocardium, New York State J. of Med. 45:

983, 1945.

21. Russek, H. L, Southworth, J. L., and Zohman, B. L.: Continuous Caudal Anesthesia as a

Test in the Selection of Hypertensive Patients for Sympathectomy, J. A. M. A. 128;
1225, 1945.

22. Russek, H. I., Southworth, J. L., and Zohman, B. L.: Selection of Hypertensive Patients

for Sympathectomy, J. A. M. A, 130; 937, 1946.

23. Smithwick, R. H.: A Technic for Splanchnic Resection for Hypertension; Preliminary

Report, Surgery 7: 1, 1940.

24. Herringham, W. P., and Wills, W. .A.: On the Elasticity of the Aorta; Being a Contribu-

tion to the Study of Arterial Sclerosis, Trans. Med.-Chir. Soc. Edinburgh 69: 499, 1904.

25. Page, I. H.; .Arteriosclerosis and Lipoid Metabolism In Ageing and Degenerative Di.seases

Biol. Symposia 11; 43, 1945.

THE T WAVE OF THE PRECORDIAL ELECTROCARDIOGRAM
AT DIFFERENT AGE LEVELS

Ramon M. Suarez, M.D., and Ramon M. Suarez, Jr., A^.D.

San^-uan, Puerto Rico

T his paper is the first of a series dealing with the electrocardiographic study
of 161 healthy Puerto Ricans. The subjects studied included 50 soldiers
between 19 and 46 years of age; 31 women between the ages of 19 and 45 selected
from the technical, nursing, and secretarial personnel of the University Hospital
at San Juan, Puerto Rico; 20 young boys and 20 young girls ranging in age be-
tween 12 and 18 j^ears; and 20 male and 20 female children between the ages of 5
and 11, most of them inmates of the Boys’ and Girls' Charity Schools of our In-
sular Department of Health. All subjects were in an apparently normal state
of health, with negative serologies, no histories of rheumatic arthritis, and no
evidences of valvular heart lesion.

The standard leads were taken first in each case. Potential variations of
the right arm (VR), the left arm (VL), the left leg (VF), and of the six precordial
points were obtained by pairing an exploring electrode with a central terminal
connected to the right arm, the left arm, and the left leg through a resistance of
5,000 ohms each. Wilson’s central terminal wdth Goldberger’s modification for
augmented limb leads was used.

In taking the extremity and precordial leads, the connections of the galva-
nometer were so made that an upward deflection represented positivity of the
exploring electrode and a downward deflection, negativity. The standard and
extremity potentials were taken at normal sensitivity of the string (1 cm. = 1 mv.)
and the precordial potentials at half normal sensitivity (1 cm. = 2 mv.). The
six precordial points used were those specified by the Committee on Precordial
Leads of the American and of the British Heart Association.^ All tracings
were made between 9 and 12 A. M. with the subjects in the reclining position.

We did not include older persons in our investigation, as the work of Willius,*
Levitt,^ Taran and Kaye,^ Warnecke,® and Gelman and Brown® have proved con-
clusively that no less than 25 per cent of these subjects show distinct electro-
cardiographic abnormalities. Taran and Kaye, in their study of 102 men and
women between 60 and 90 years of age, reported abnormal T waves in one-fourth
of them. These findings were most commonly observed in the ninth decade and
less often in the eighth, the most frequent finding being a negative T4. Abnormal
findings were as frequent in women as in men. The aged, therefore, cannot be
considered normal individuals from a cardiovascular standpoint.

From the School of Tropical Medicine and the Mimiya Ho.spital.

Received for publication Jan. 25. 1940.

480

SUAREZ AND SUAREZ, JR.; T WAVE OF PKECORDIAL ECO

483

, Electrocardiographic studies pf young adults have been performed by
several investigators. We shall mention here Shanno,' who studied 100 student
nurses of 18 to 22 years of age with the conventional leads and the precordial
electrocardiograms CFi and CFc; Larsen and Skulason,® who analyzed the ex-
tremity deviations from 50 men and 50 women; Deeds and Barnes,^ who studied

Fig. 1. — A, Case 776. P. R., aged 28 years, male. Negative T wave only in Vi. n. Case. 787.
M. H., aged 28 years, male. Negative T wave only in V,. Both cases arc typical of the electrocardio-
graphic pattern of adult males.

the characteristics of the chest lead electrocardiograms of 100 norma! adults
and claim that CR is better than CL and CF. In one instance they found that
the T wave approached negativity in Lead CF 2 , but this never occurred in CR;.
Thomas^'’ concludes that “until the limits of normal variation in the human elec-
trocardiogram have been much more thoroughly explored, the diagnosis of heart

482

AMERICAN HEART JOURNAL

disease in young persons should seldom be basgd on electrocardiographic findings
alone, in the absence of clinical manifestations.” In an analysis of electrocardio-
grams obtained from 1,000 healthy aviators, Graj’^biel, McFarland, Gates, and
Webster” utilized only the three standard leads and Lead IV F. In the latter
they found that the T wave was upright in all but two instances, when it was

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aged 19 years, female. Inverted T wave in Vj, diphasic in Vn.

U.

diphasic. The range of the T wave ivas 1 to 15 mm. and the mean, 5.9 millimeter.
Huge T waves, they state, are rarely observed in healthy persons. Kossman and
Johnston” studied 30 subjects and published their table of normal values of the
ventricular deflections for the standard and unipolar special leads.

SXjAREZ AND SUAREZ, JR. : T WAVE OF PRECORDIAL ECG 483

. Fetal electrocardiograms have rarely been taken with special apparatus, and
electrocardiographic studies in children have not been numerous. Lepeschkin^-*
studied the normal chest electrocardiogram in 50 children from 2 weeks to 15
years of age. “The T wave,” he says, “is inverted on the right chest anteriorly
and upright on the left. On transition, a diphasic T is found. This transition
is more to the left anteriorly in children than in grownups, and this deviation
from the midline is greater the younger the child. These differences are related
to the more lateral position of the interventricular groove in the younger child.”
Gelman and Brown® reported the electrocardiograms of 121 normal children
between 12 and 14 years of age and compared them with a group of “normals”
over the age of 61. These authors used only the three conventional leads.

3 .•« V K S** SS rf

^2 .

the St
ras m
roach
he he
mome
negat

elect
er w
'ho ha
:al he;

484

AMERICAN HEART JOURNAL

conditions,” they say, ‘‘two different chest electrocardiograms — the left and the
right ahvaj's exist, the newborn seem to show immediately after birth, usually
over the whole thorax, only one pattern, that of the right chest electrocardiogram.
This pattern changes in the left axillary line generally after a few hours, but

, aged 18 years,
lomale Jlegal
alt pattern of tli

T wave may
variations ii
le main rece
g ventriculai
Many phy

A.MEKICAN HEART JOURNAL

}SS

Tabm: I. T-\Va\t; Shapk*

Af'i; A.Mi sex j NO. ■ j ^’l 1

! \'j 1 V, 1 \\ :

Vs

j

\'c

■ ( ■ 1

Male adult'- i 50

19-46 \ r. !

1

1 32 R

1 10 r

' 7Di:l

1 iD+i
; 1

1 45 R i

1 F '
• 4 D +

]

48 R

2 P '

1

44 R

6 P

47 R

3 P

50 R

rt male adults : 31

19-45 vr. !

1 20 R

: s F

< 2D -f

1 D

27 R

2 F

1 D

I P

28 R -
2 F

2 P

]

31 R

31 R

31 R

Male Eoung.=ter« * 20
12-18 yr.

1

i

' !

19 R

1 D

1 i

1 1

12 R

1 F

5 D

1 P

I Nt.

12 R

5 D

2 D

1 P

2 Nt.

18 R

2 D !

20 R

1

20 R

f'etnale voiingstcrs |

12-18 vr. 1

•

20 !

H

14 R

2 F

1 D

IS R

1 F

1 Nt.

i 20 R

20 R

20 R

Male cliilfireri

5-11 yr.

20

18 R

2 D

9 R

11 D

9 R

10 D

1 Nt.

19 R

1 D

19 R

1 P

19 R

1 P

20 R

1

i 13 R

7 D

15 R

1 F

4 D

18 R

1 F

1 D

■

19 R
t P

*R =• RouikIkI, 1' flat; D = diphasic; P = pointed; Nt. *= notcliod.

'I'Ani-K 11. T-\\’avh Duration (In Seconds)

AGE AND SEX 1

NO. j

Dura-

tion

‘ 1

1

1

\'6

^■c

Male adults

1

50

Min.

0.08

0.14

ra

1

0.18

0.16

0. 12

19-46 yr.

Ma.x.

0.26

0.27

0..52

0.30

0.24

I

Av.

0.16

0.21

mm

0.23

0.22

0.21

Female adult'-

i

Min. i

0.06

0.08 i

0.10

0.12

0.12

0. 12

19-45 yr.

Ma.\.

.\v.

0.20

0.136

1

0.24 i
0.167

0.28

0.196

0.28 1
0.190 ;

0.24

0.181

0 20
0.161

.Male voum;-.tc'rs

20 1

Min.

0.04

0,08 i

0.08

mm

0.10

12-18 yr.

Max.

0.20 1

0.28

0.28

mSSm

mSm

0.20

A^^

0,117 1

1

0.177

0.196

wB

0.154

Female youngsters ’

20 ;

Min.

O.'OS

0.12

0.16

0.12

0.12

12-18 yr.

r

Max.

0.20

0.24

0.24

0.24

0.20

1

Av.

0.155

0.175

1 0.175

0.167

0.155

-Male ciiildren i

20 !

Min. !

0.12 j

0.08

0.08

0.10

0.16

a-la yr.

I

Max.

0.18

O.IS

0.24

0.24

0.24

HnlJI

1

.\v.

0.128 i

0.141

0.142

0.179

0.191

Female children

20 '

Min.

0 12

0.08

0.08

mm

mm

5-15 yr.

Max.

1 0.18

0.16

0.26

’

Av.

1 0.149 i

\

0. 136

0.157

H

0.178 j

1

n

SUAREZ AND SUAREZ, JR.: T WAVE OF PRECORDIAL ECG 489

of repolarization of the ventricular muscle is due to a difference in temperature;
they are inclined to accept the suggestion of Dr. A. C. Young to the effect that
the subendocardial muscle; layers, being probably subjected to a higher pressure
during systole than the subepicardial, may repolarize more slowly, particularly
in the left ventricle and left side of the septum.

The ascending limb of the T wave rises slowly and inscribes a slight upward
concavity; the descending limb comes down more abruptly. The apex, or peak,
is therefore at a slightly greater distance from the base of the ascending limb
than from that of the descending limb. In the negative wave, the descending
limb descends more slowly with a tendency to inscribe an upward convexity,
while the ascending limb rises more abruptly. The apex, or peak here, is farther
away from the base of the descending limb than from that of the ascending limb.
This apex, or peak, may be sharp and pointed, or more or less blunt. The wave
may appear positive, isoelectric, diphasic, or negative.

Table I shows the shape or form of the T wave at the various precordial
points: Vi, V2, V3, Vi, V5, and Vq. "R” represents both the positive and
negative T waves, when they are blunt or rounded. “F” represents the flat or
isoelectric T waves; “D” the diphasic; “Nt.” the notched; and “P” represents
the pointed T waves of high voltage. In Vi, both the children and the young
boys and girls showed rounded T waves while only 64 per cent of the male a
per cent of the female adults did. On the other hand, almost all the male and
female adults showed the normal concavity of the T wave in V2, while only 60
per cent of the'young boys, 70 per cent of the young girls, 45 per cent of the male
and 65 per cent of the female children showed this form of T wave. The number
of flat and diphasic T waves, which were more frequently observed at points V2
and V3, diminished when we advanced to the left side of the heart so that in Vc,
all T waves appeared rounded or blunt in shape, except for one pointed T wave
in the group of male and another in the group of female children. Most of the
pointed and high T waves were observed in V3, V4, and V5 of the group of male
adults. There were more diphasic T waves in Vo and V3 of the’ group of male
children than in any other group.

Although the duration of the T wave is probably of no particular importance
and is difficult to measure accurately, we are reporting our findings in Table II.
The duration of the T wave appears to be always less in Vi than in Ve of all groups,
and slightly longer in the group of male adults than in all the other groups.

The voltage of the T wave appears in Table III. Each millimeter represents
0.20 millivolt. In order to express our results in millivolts, we would have to
multiply the figures by 0.2. The highest T wave was 6.25 mm. in V4 of the group
of male adults; the lowest, —4.25 in Vo of the group of male children. The
wave appeared highest in V4 and V5 than at the other points, and higher in the
adult males than, in the adult females, and in the group of children than in the
group of young boys and girls. The children and the adult males, therefore,
exhibited the highest T waves in this series. Vfith only one or two exceptions,
.the negative T wave was lower in Vi than in V2. This is not the usual finding in
coronary thrombosis.

amhricax heart jourxae

m

In 7'able we have arranged the number of positive, negative, diphasic,
and flat T waves found in the various groups. In V], 18 men (36 per cent)
and 16 women (51 per cent), 13 young boys (64 per cent) and 17 young girls

r\m r in. T-Wwr, Voltage in MtLLiMETERS (1 m.m. = 0.20 >iu.)

!

i:LX 5

j

NO

voltage

; Vs

V 4

NLiIe Adults '

50

Min.

Ma.'v.

-2.5

2.5

05

5.25

1.25

6.00

2.00

6.25

1.25

5.00

0.50

4.00

1

—

Female achihb 1

19-45 \r. j

31

Min.

i\Iax.

-1.50

2.25

i -1.25
3.00

-0.25
3.50 ;

1.25 1
4.00 j

I.OO

3.50

1 1.00
! 2.50

.Male \ounKsler.-- |

12-18 \r.

20

1

Min.
Ala.v. 1

-2.50

1.25

-2.50

4.50

-0.75

4 25

1.00

4.00

1.00

4.50

1.00

4,25

Female voungstcr";
l 2 -) 8 yr.

20

Ivlin.

Max.

-1.25

1.00

—0.75 '
3.00 '

-0 50

2 25

0.50

3.00

1.00

2.75

0.50

2.50

Male children

5-11 yr.

20

Min.

Max.

-3.75

-0.75

-3.00

1.50

|[^

1 50

5 00

2.00

5.75

Female children

5-11

20

i

!

Min.

Max.

-3.00

- 1.00

— 2 75
1.25

-2 00
3.00

-1.50

5.25

- 1.00

5 00

1.25

3.50

Tadle IV. T Wave; Number of Positive, Negative, Diphasic, and Flat T Waves

AGE AND SEX. |

j

NO. j

1

1

V. 1

1

\’s

V,

\'s

H

i

Male adults |

19-46 yr. !

i

^50

18 -(36%)

: 8 D

10 F

14 -f .

1

0- i

4 D

1 F ,

45 “f*

All -f

1

! All 4-

All 4-

i

All 4-

Female adult's

19-45 yr.

- 1

31

1

16 -f51%)

1 3D

8 F

! 4 -f

1

4 -

1 D

2 F

24 + 1

1 -

2 F

28 -f

All 4-

i

1

All 4-

1

All 4-

%

Male voungsters,

12-18 >T.

1 13 -(64%1 1

1 1 D

! 1

6 + :

4 -

5 D !

1 1 F 1

10 -4-

1 - i

1 5 D j

j 14 4-

0 -
2 D i

i

i

All 4- I

All 4-

Female I’oimpster!, ,
12-18 yr.

! 20 i

f

1

1 '

i 17 -(85%) 1

: ID 1

2 F i

1 0 -f 1

2 - i

1 D !

2 F i

15 + 1

■

1 ‘

‘ 1

All 4- 1

All 4-

.Ml 4-

Male children

5-11 yr.

! 18 -(90%1

1 2 D !

0 -f" '

9 -

11 D 1
0 -f-

i 6 -

10 D

4 4-

1 -
1 D
18^

1

All 4-

All 4-

Female children

5- 1 1 yr.

1 20

!

20 -(100%)

■

13 -
7 D i
1 0 -F

?

8 - ,
4 D :
1 1 F

1 / 4- '

f5

1 1 F
j 15 4- ‘

i

19 4-

1

All 4-

SUj\REZ and SUAREZ, JR.; T WAVE OF PRECORDIAL ECG 491

(85 per cent), and 18 male (90 per cent) and 20 female (100 per cent) children
showed a negative T wave.

In V2, there was no negative T wave for the group of male adults, but
there were four diphasic and one isoelectric T wave. There were four negative T
waves .(13 per cent) in the group of female adults, with one diphasic and two
flat or isoelectric; four (20 per cent) in the group of young boys, with five diphasic
and one flat; two negative with one diphasic and two flat in the group of young
' girls; nine negative T. waves (45 per cent) in the male children, with 11 diphasic;
and 13 negative T waves (64 per cent), with seven diphasic in the group of female
children. The frequency of negative T waves diminished rapidly from to
Vc, and there was not a single instance of negative T waves in Vg.

In the group of male adults, negative T waves were observed only in Vi
(Figs. 1, 2, and 3). The groups of female adults and of the young boys and girls
presented negative T waves in Vi, Vo, and Vg. Several women between the ages
of 18 and 34 showed negative T waves in Vi and Vo. The male children pre-
sented negative T waves as far to the left as point V4, one female child reaching
point V5.

In general, it may be stated that negative T waves in the precordial electro-
cardiogram are more frequent in the female than in the male sex, except at the
age level between 12 and 18 years, at which the incidence is similar. This may be
explained by the fact that girls betAveen 12 and 18 are more mature physically
than boys of the same age.

Table V gives the percentages of all negative, diphasic, and flat T waves
found at the various precordial points. The similarity existing beween the
groups of young girls and of the women, and the difference between the precordial
electrocardiogram of the young boys and of the men, is again evident. Children,
male and female, gave similar percentages, but there appears to be a slight tend-
ency to more negative T waves in the girls.

Table V. T Wave; Percentage of Negative, Diphasic, and Flat T Waves

AGE AND SEX '

NO.

V,

V:

V,

...

Ve

Male adults

19-46 yr.

50

10

0

0

0

0

Female adults

19-45 yr.

31

22

.

9

0

0

— - — -- 1 - ■

0

Male youngsters
12-18 yr.

20

70

50

30

5

0

0

Female voungsters
12-18 yr.

20

95

25

10

0

0

0

Male children
: 5-11 yr.^

20

100

80

5

0

0

Female children

20

100

65

25

5

0

5-1 1 yr.

492

A^rERICA^■ HEART JOURNAL

T-vni-t: \'I. S-T Skgmknt; Kumbkr of Cases akd Number ix jim. Above
OR Below the Isoelectric Like

age and sex

1

j NO.

' N’,

1

:

f

\'.i

1 V.

1

i v„

1

1

Male adults

19-46 yr.

; 50

1

,4+1

j

6+ 1
1+1.5

1

1

7+ 1

1+ 1.5

I 7+1

1

!

i

I 1+15

; i-i

t

1

I'ernalc adults

19-45 yr.

!

1

1 2+ 1

1

1 1+1
j 2 -i- 0.5 j

1+1

1 - 0.5

0

1 + 1

1 + 1.25

1 + 0 5

1+1

1 + 05

1

1 1+05

Female youngsters I
12-18 yr. |

! 20

!

2+ 1

1 + 0.5;

1 + 1

2 + 0.5

5+05

2 + 0.5

j 1 + 05'

1 + 0.5

.Male cliildren j

5-11 3T. j

20

1

0

0

0

0

1

i 0 j

0

Female children j

5-11 yr. j

20

1 + 0.5

1

, 3+0.5

1 i

2+0 5

1 ^

i 1

1 ' '

1 + 05

1

1 + 1

1 + 05

0

2+ 0.5

Only one case below isoelectric line -1 mm. in Vo in a male adult.

Only two cases more than 1 mm. above Isoelectric line (+1.25 mm.V, in male youngster (18 years of
agei and one male adult (+1 5 mm.).

S-T segment on line in all male cliildren from 5 to 11 years of age.

Female children of the same ago group showed slight deviation. •

Table VI reveals that deviation of the S-T segment from the isoelectric
line was a relative!}'’ rare finding. Only one case, a male adult, showed negative
deviation of 1 mm. (at point 6). (The boys from 5 to 11 years showed no dev-
iation of the S-T segment. The highest deviation (-f 1.5 mm.) was observed
once in the group of male adults, but the usual deviation was from -f0.50 to
-fl millimeter.

We are also presenting the precordial electrocardiograms, obtained from
two subjects of each of the groups studied, which show the various patterns at
different age levels and the pronounced fluctuations in the T waves of different
subjects of the same, or appro.ximate, age (Figs. 1 to 7). The legend for each
figure is self-explanatory.

SUMDLVRY AND CONCLUSIONS

We have presented a study of the T wave of the unipolar precordial electro-
cardiogram in 161 healthy Puerto Ricans, both male and female, between the
ages of 5 and 46 years.

The form and voltage of the T wave, as well as the deviation of the S-T
segment from the isopotential line, have been determined.

The study suggests that, independent of age levels and sex, a negative T
wave in Vi may be considered normal, and a negative T wave in Vo should be
considered abnormal.

In the male adult of o\'er 19 years of age, a negative T wave in Vs, Va, V.),
Vj, and Vo is probably abnormal, especially at the last four points. In the adult

SUAREZ AND SUAREZ, JR.: T WAVE OF PRECORDTAL ECG 493

female of the same age, and in the young girls and boys 12 to 18 years of age,
a negative T wave in V4, V5, and Vc may be considered abnormal. In children
from 5 to 11 years, a negative T wave is probably abnormal only when present
in -Vc and perhaps V5.

Deviations of the S-T segment in the precordial electrocardiogram should
be considered normal when such deviation is positive and does not go over 1.5 mm.
in the adult or above 1 -mm. in children. An S-T segment 1mm. below the iso-
electric line was found only once — at point 6, in a male adult.

This stud}'- further suggests that, in addition to age and se.x and such physi-
ologic factors as cold, change of position, digestion, and nervous disturbances,
there are other, j’^et undetermined, intrinsic factors that may influence the T wave
of the precordial electrocardiogram in normal persons.

We are indebted to Dr, Frank N. Wilson, of Ann ."^rbor, Michigan, for having read this
manuscript and offered valuable suggestions.

REFERENCES

1. Standardization of the Precordial Leads; Supplementary Report, Am. He.\rt J. I.t: 235,
1938.

2. Wiilius, F. A.: The Heart in Old Age, Am. J. M. Sc. 182: 1, 1931.

3. Levitt, George: The Electrocardiogram in the Aged, Am. Heart J. 18; 692, 1939.

4. Taran, Leo M., and Kaye, Milton: Electrocardiographic Studies in Old Age, Ann. Int.
Med. 20; 954, 1944.

5. Warnecke, B,: The Electrocardiogram in Apparently Non-Cardiacs Over 65 Years of Age,
Ztschr. f. Kreislaufforsch 31; 391, 1931.

6. Gelman, L, and Brown, S.: Electrocardiographical Characterization of the Heart in Old
Age and -in Childhood, Acta med. Scandinav. 91; 378, 1937.

7. Shanno, Ralph L.: Variations in Normal Precordial Electrocardiograms, Am. Heart J.
19: 713, 1940.

8. Larsen, Kaj, and Skulason, Th.: The Normal Electrocardiogram. 1. .Analysis of the E.x-
tremity Derivations From 100 Normal Persons Whose .Ages Ranged From 30 to 50 Years,
Am. Heart j. 22; 625, 1941.

9. Deeds, Douglas, and Barnes, Arlie R.: The Characteristics of the Chest Lead Electro-
cardiograms of 100 Normal Adults, Am. He.art J. 20; 261, 1940.

10. Thomas, C. B.: The Significance of Electrocardiographic Abnormalities in Young Adults,
Bull. Johns Hopkins Hosp. 74; 229, 1944.

11. Graybiel, Ashton, McFarland, Ross A., Gates, Donald, and Webster, Fred: .Analysis of
the Electrocardiograms Obtained From 1,000 Young Healthv Aviators, .Am. Heart J. 27;
524, 1944.

12. Kossman, C. E., and Johnston, Franklin D.: The Precordial Electrocardiogram. I. The
Potential Variations of the Precordium and of the Extremities in Normal Subjects, .Am.
Heart J. 10; 925, 1935.

13. Bell, G. H.: The Human Fetal Electrocardiogram, J. Obst. & Gvnaec. Brit. Emp. 45:
802, 1938.

14. Lepeschkin, E.: The Normal Chest Electrocardiogram in Childhood, Arch. f. Kreis-
laufforsch. 3; 321, 1938.

15. Master, Arthur M., Dack, Simon, and Jaffe, Harry L.: The Precordial Lead in Children.
Presented at the Annual Scientific Meeting of the New A''ork Committee on Cardiac
Clinics, New York, N. Y., April 28, 1936.

16. Groedel, F. M., Kisch, B., and Reichert, P.: Changes in the Standard Electrocardiogram
and the Chest Leads During the First Stages of Life, Cardiologia 6; 1, 1942.

17. Groedel, F. M., and Miller, Max: Electrocardiographic Studies in the Newborn, Exper.
Med. &Surg. 2; 110, 1944.

18. Wilson, Frank N,, and Finch, R.: Effect of Drinking Iced-Water Upon Form of T Deflec-
tion of Electrocardiogram, Heart 10: 275, 1923.

19. .Ashman, R., and Hull, E.: Essentials of Electricardiography, New York, 1944, The Mac-
millan, Co.

DISAD\'ANTAGES OF THIOURACIL TREATMENT OF
ANGINA PECTORIS

Joseph R. DiPalma, M.D., axd John J. MaGovern, M.D.
Brooklyn, N. Y,

D espite the numerous reports'"® concerning the beneficial results to be
obtained b}'^ total thyroidectomy for angina pectoris, this procedure has
gained small popularity. With the advent of thiouracil,' a drug capable of lower-
ing oxygen consumption, even when the thyroid gland is normal,®-® a means be-
came available to reinvestigate this problem.

In 1944 we began to administer thiouracil to a limited number of cardiac
patients with proved coronary arterj^ disease and severe angina pectoris, keeping
close watch on the level of o.vygen consumption, the degree of anginal pain, and
the exercise tolerance. Since then a publication'® has appeared which reports
startlingly good results from this type of therapy. Our own results are not
encouraging for the reasons to be outlined below, and it appears desirable to
record them.

METHOD.S

Only patients who had been observed both on the wards and in cardiac
clinic for several years were studied. This was desirable so that the subjective
symptoms of angina pectoris might be better evaluated. E\'ery clinician is
acquainted with the variability of anginal pain, changing as it does with the
season and the frame of mind of the patient. We desired to make sure of the
consistenc}' of the anginal pain of our patients by the best means available:
a close personal acquaintance with the patient over an extended period of time.

All of the eight male patients included in this report had severe coronary
artery disease. Electrocardiographic and clinical evidence indicated that six
of them had had coronary occlusions with myocardial infarctions one to two years
previous to the time of our study. The remaining two patients (Table I) gave
no history of myocardial infarction. One patient, F. P., had a normal electro-
cardiogram at rest. However, after exercise the tracing showed marked depres-
sion of the S-T segment in Lead II, indicating marked mjmcardial ischemia.
Moreover, both the systolic and diastolic blood pressure always fell after exercise.
The second patient, L. P., was the only one of the group with a valvular lesion.
He had severe rheumatic heart disease with marked aortic insufficiency. The

till' Doiwriini'iit of Moiliciup, Lonj; IslamI C'oUpsp of .Mtilicliip, KinRS County Ho.-ipitnl

Division.

. Ri'ceiVfd for publication Ki-b. 2s. l!Hf>.

404

Table I. Results ok Thioukacil 'rFtERAPv in Eight Noniiypertensive Cardiac F’atients

ArtcriosoIcrotiV 0.6 to 1.2 I yr., j .T040 j 13,266 | 0 —22 Limited improve- Fair Statius angiiiosis; no real relief

heart disease L> mo. j ! ment | except at my.vedema IcVel .

496

AMERICAN HEART JOURNAL

s)- 5 toiic blood pressure was 190 on the average; the diastolic pressure could not
be determined since the sounds were still audible at zero. An electrocardiogram
showed right bundle branch block. This, with the low diastolic pressure, may
be taken as good evidence of mj'ocardial ischemia. None of the patients were
In^pertensive.

Anginal pain was arbitrarilj'- determined by assigning four degrees of severity
nf pain for each patient. Naturally, a 4 plus degree of pain for a patient with
mild angina was not comparable to a 4 plus degree of pain in the patient with
most severe angina. In grading the degree of pain, due consideration was given
to the frequency of use of nitroglycerine and to various psychic influences.

An exercise test was done at suitable intervals, usually in the morning, two
hours after a light breakfast. A single step nine inches high was used. The
patient was always e.xercised at the rate of 20 to 25 steps per minute. Environ-
mental temperature was kept at 70 to 74° F. Exercise was stopped only at the
point of severe anginal pain. We found the exercise test particularly valuable
because it enabled us to select patients from the viewpoint of angina rather than
dyspnea as a limiting point to their exercise. The results were calculated in
foot-pounds to obviate the factor of weight. Obviously a patient weighing
200 pounds doing 20 steps has done more work than a patient weighing 150
pounds doing the same number of steps. Also, with a lowering of the basal
metabolic rate, the patients gain weight, and calculation of the results in foot-
pounds of work done eliminates an obvious error from this factor.

Blood pressure and pulse rates at rest, immediately after e.xercise, and at
interv'als of two, four, and eight minutes after e.xercise were also taken. Since
therapy had little effect upon these figures, they will not be reported.

ThiouraciP was generally administered in daily doses of 0.6 Gm. divided
into three 0.2 Gm. portions. As much as 1.2 Gm. in divided daily doses was
given to one patient (N. S.), but only while he Avas hospitalized. The patients
were AA'arned to Avatch for throat infections, fever, or rashes. They AA^ere seen
Aveekly to prevent the signs and symptoms of agranulocytosis from escaping
notice. None of them had palpable thyroid glands nor did any have the symp-
toms of hyperthyroidism. Patient F. T. (Table I) had an initial basal metabolic
rate of -f-55 and may have had masked hyperthyroidism.

Placebo tablets resembling in every AA'ay the thiouracil tablets AA'ere used
on tAvo occasions to test the result of cessation of therapy Avithout the patients’
knoAvledge. These contained only small amounts of urea and magnesium sulfate
to simulate the taste of thiouracil.

RESULTS

One of the first features to strike our attention Avas the refractory nature
of the normal adult thryroid gland to thiouracil. This Avas particularly true
Avhen the control basal metabolic rate AA^as near the zero level. In Table I it
may bo seen that patient F. P., after two months of 0.6 Gm. of thiouracil daily,

*l!oUi tho thiouracil anti the placebo tablets used in this study w cre supplied llirouBh the {reiieroslty
of Ur. Stanton H. Hardy of the Lederle I.aboratorles, Inc., Pearl River, N. V.

■ Dl PALMA AND MA GOVERN : DISADVANTAGES OF THIOURACIL 497

had a drop of only from +9 to —11. Similarly, patient I. F. actually had a rise
in the basal metabolic rate of from —7 to +22 on the same dosage. In his
case considerable dyspnea was present during the final basal metabolic rate
determination. This, however, we believe to be the result of a tendency of
thiouracil to cause- water retention f for this reason the result is valid and is
properly included. In the case of M. G., therapy had to be stopped after three
weeks because of a marked allergy to thiouracil. He developed a severe maculo-
papular rash which disappeared in two days. On restarting thiouracil the rash
reappeared and therapy had to be terminated. Patient F. P. also developed a
much more severe maculopapular rash with scaling, and therapy had to be
stopped. It is interesting that in this latter case the rash occurred after thiouracil
had been given for two months. Patient L. P. had a fall of the basal metabolic
rate of from +10 to —10 on 0.6 Gm. of thiouracil daily for three and one-half
weeks. In his case therapy had to be terminated because he acquired a severe
constricting sensation in the chest and marked dyspnea, both exertional and
nocturnal. In his case also we feel that the thiouracil caused water retention
and incipient pulmonary edema, particularly in view of the severe aortic in-
sufficiency.

In these four patients there was no real improvement in the degree of
anginal pain. In the first three patients (Table I) exercise tolerance did not im-
prove beyond - what could be expected from training. The fourth patient,
L. P., had an increase in exercise tolerance of from 7,380 foot-pounds to 30,012
foot-pounds. However, at the end of three weeks of therapy, he could not exer-
cise at all because of dyspnea, so that no real gain was made.

The next four patients were treated for periods over one year and their
cases will be described in detail.

Case F. T. (Table I and Fig. 1). — Treatment was started on this patient in the middle of
October, 1944. There was a marked fall in basal metabolic rate of from -{-55 to —22 after
0.6 Gm. of thiouracil daily for nine weeks. He did not suffer from Graves’ disease so far as
could be determined clinically. However, the elevated metabolism and especially the sensi-
tivity to thiouracil strongly suggested that he had masked hyperthyroidism. The exercise
tolerance quadrupled in the same period, and there was a marked diminution in precordial pain.
Before therapy he had been using nitroglycerine daily; after therapy was started, it was required
only occasionally. Toward the end of December he was put on placebo tablets for eight weeks.
The metabolism then rose to —3. The exercise tolerance continued to improve, then fell sharply
at the end of this period; that is, toward the last week of February. The precordial pain remained
improved despite the rise in metabolism. He was again started on 0.6 Gm. of thiouracil daily
to study the effects of a further lowering of metabolism. This time the thiouracil was continued
without interruption for four months, until the end of June. The metabolic rate fell much more
slowly this time, starting from a level of —7 and falling to —35 at the end of the period. He
acquired definite symptoms of myxedema with a gain of 20 pounds in weight, lethargx’, puffy
face, and hoarse voice. The exercise tolerance improved at first during the months of March
and April but fell gradually during May and June to pretherapy levels. The precordial pain
disappeared completely from the end of March through July. In the exercise tolerance test, it
is noteworthy that the limiting factor to exercise changed from prccordial pain to dj-spnea. An-
other interesting development was the onset of severe intermittent claudication during the period
of the greatest depression of metabolism. Naturally, during this period the limiting factor to
exercise was calf pain. This is explained by the marked diminution of peripheral blood flow which

498 AMEIUCAX HEART JOURNAL

is known to occur in myxedema.** During August and September thiouracil was not given.
The metabolism promptly rose to zero in six weeks' time. The prerordial pain returned. The
e.xercise tolerance, howcv’cr, did not improve appreciably.

Pig. 1 — Effect. s of treatment in Patient K. T.

In summary, it may be said that the patient felt best and could do most
when the basal metabolic rate was maintained between — 10 and — 20. Upon

DI PALMA 'AND MA GO^^I;RN : DISADVANTAGES OF THIOURACII, 499

cessation of thiouracil, his symptoms returned with the rising metabolism so
that no real gain was made.

Case L. F. (Table I and Fig. 2). — This patient had a control basal metabolic rate of +25 in
November. With only four weeks’ therapy with 0.6 Gm. of thiouracil daily, the basal nietabolic
rate fell to —15 in December. In this period, precordial pain diminished markedly and the exer-
ci.se tolerance nearly tripled. When placed on placebo tablets, the metabolism rose to +8, fell
to —6, and finally rose again to +8. At this time the exercise tolerance showed a closed inverse
relationship to the level of metabolism. This was the only instance in the series in which it was
possible to demonstrate clearly that when the level of metabolism rises, the ability to exercise
falls, and vice versa. With the rise in metabolism the precordial pain returned. 'He was then
put back on 0.6 Grii. of thiouracil daily in February. This was continued until May, when it
was cut to 0.3 Gm. daily for one month, then raised to 0.4 Gm. daily until October. On these
doses the metabolic rate was maintained at about —10. Precordial pain dhsappeared completely
and the exercise tolerance improved steadily. The patient expressed great satisfaction and was
able to return to light work for the first time in two years.

It must be pointed out in this case, however, that the thiouracil must be
continued and the patient must be carefully watched to maintain the good results.

Case N. S; (Table I and Fig. 3). — This was our patient with the most sev'cre angina. He
could only walk about fifty feet before he was .seized with agonizing precordial pain. The control' .
basal metabolic rate was zero. Starting in November, he was put on 0.8 Gm. of thiouracil daily
for two weeks, then on 0.6 Gm. daily for two more weeks. Tlie thiouracil then had to be stopped
because of a severe upper respiratory infection. On this course of therapy the metabolism fell •:

to —16. There was no change in precordial pain and exercise tolerance. It was decided to
hospitalize him in January to give him an adequate course of thiouracil under close observation.
He was given up to 1.2 Gm. of thiouracil daily in four doses for three weeks. This wa.s then cut
to 0.8 Gmv daily and maintained over a period of four and one-half months. At this time, in
June, the drug had to be terminated because of the onset of severe nocturnal and exertional dysp-
nea. On this strenous therapy the precordial pain diminished but little, although the metabolic
rate attained a low of —20. The exercise tolerance improved up until .^pril, when it had more

500

AMERICAX HEART JOURNAL

than tripled. -After this period, ability to do e.xercise diminished gradually to control levels,
fn July the thioiiracii was again started at a dosage level of 0.8 Gm. daily. In this instance the
metabolic rate fell from +7 to —22, at which time (September) he had all the clinical signs of
mv-Ncdema. In the entire one-year period, it was onh' at this time that he c.xperienced any
appreciable relief in the precordial pain. Ability to do e.xercise, however, was markedly curtailed
because of the onset of severe intermittent claudication.

In summary, this patient with severe angina pectoris proved to be markedly
refractory to thiouracil. A total dose of 209 Gm. of thiouracil over a period of
250 days was required to depress the basal metabolic rate to my.vedema levels.
Noteworthy is the fact that the control metabolic rate was zero. This brings
out the point that the lower the metabolic rate is to begin with, the more difficult
it is to depress it with thiouracil. No real gains were made either in improving
the degree of precordial pain or in increasing exercise tolerance.

Case J. K. (Table I and Fig. 4). — This patient had the least anginal pain of the group. He
could walk from five to seven city blocks without pain. The control basal metabolic rate was
the lowest of the group, —10. He also proved to be refractory to thiouracil. Daily dosage of
from 0.6 to 0.8 Gm. only lowered the metabolic rate to —17 over a three-month period. The
exercise tolerance more than doubled during this period. On the whole, the precordial pain dimin-

Fig. 4. — Efrec(.s of treatment Jn Patient J. IC.

ished considerably, although he still experienced occasional severe attacks. Thiouracil was
continued at 0.8 Gin. daily for four more months, until June, with two brief, free periods because
of upper respiratory infections. The metabolic rate was not depressed but rose to —10 at the
end of the period. For no apparent reason the e.xercise tolerance also diminished. In July he
began to experience severe attacks of precordial pain . At the end of this month the pain became
sulicternal in type and he was hospitalized for a period of bed rest and study. Three serial
electrocardiograms did not reveal ch.inges indicative of coronary occlusion, but the sedimentation
ate was elevated and lie had temperature ri.sc to 101.4° F. which could not be e.xplaincd. It

DI PALMA AND MA GOVERN: DISADVANTAGES OF THIOURACIL oOl

was therefore considered wise to treat him for myocardial infarction even in the absence of abso-
lute proof. The precordial pain remained severe for the next four months in spite of the fact that
readministration of thiouracii depressed the metabolic rate to — 16. When he was again exercised
in October, he had returned to control levels.

In summary, this patient who had a low metabolic rate to begin with and
relatively mild anginal pain may have been actually harmed by the thiouracii
therapy. During the course of therapy he experienced symptoms of coronary
occlusion. At the end of a year the anginal pain was worse and the exercise
tolerance less than when therapy was started.

DISCUSSION

One point clearly brought out by this study is that depression of the basal
metabolic rate diminishes precordial pain. This is most true in patients who have
an initially elevated metabolism. Usually to make the precordial pain disappear
completely, myxedema levels have to be attained. Thus the effects of total thy-
roidectomy on angina pectoris are reproducible by thiouracif therapy.^'®’

Does this mean that the coronary circulation is relatively enhanced in the
states of diminished thyroid activity? The evidence is greatly against this view-
point. In myxedema the cardiac output is diminished,’''* blood volume is re-
duced,’^ and the peripheral blood flow is slowed." The individual’s personality
changes. He has less drive and less energy. Glandular activity and secretion is
lessened. Intestinal absorption is slowed. Thus the beneficial results on coron-
ary circulation could be explained purely on a mechanical basis: less demands are
made upon a heart with diminished myocardial reserve. In other words, the
individual is forced to live within the limits of his myocardium’s ability to do
work.

The attractive theory that diminished thyroid activity lessens the sensitivity
of the heart to epinephrine has been enlarged upon.®-'® There is evidence against
this theory,’^-’® but, if proved true, it would be an added reason for diminishing
thyroid activity in patients with heart disease.

There are, however, many practical disadvantages to both total thyroidec-
tomy and thiouracii therapy. The difficulties of control of the basal metabolism,
by thyroidectomy have been pointed out.® Thiouracii has proved to be ratlter
toxic and no substitutes have been found for it.’® Moreover, it has to be given
for long periods of time and in large doses in order to depress the metabolism
of an individual whose metabolism is low initial^. As soon as the drug is stopped,
the metabolism rises again so that no real gain is made. The greatest difficulty
is a tendency for water retention as metabolism is lowered. In certain cardiacs
this results in pulmonary’- edema with nocturnal and exertional dyspnea.’*' Thus,

*We wore able to demoiuslrate this point clinically to our complete satisfaction. A patient with
severe hypcrten.sivo heart disease and anasarca had been observed on the ward for at least six months.
He was kept edema free only by injection of mercurials every third day and strict limitation of .salt and
fluid intake. Without changing his regimen in any way, he was given 0.6 Gm. of tliiouracil dally.
After six days he became markedly edematous and had an attack of severe pulmonary edema. The
thiouracii was stopped and he promptly recovered. Tills experiment was repeated on two subseciucnt
occasions with similar results. Thus the tendency of thiouracii therapy to cause water retention was
amply demonstrated in this patient. The basal metabolism studies were unsatisfactory because the
dyspnea obscured the re.sults.

502

AMERICAN HEART JOURNAL

one defeats his purpose in these instances because obviously the patient is in
more trouble with dyspnea than with angina.

Ii is well known that the amount of cholesterol in the blood rises with a
lowering of the metabolic rate. Naturally this predisposes to atherosclerosis,
imieed. one of our patients developed symptoms strongly suggestive of coronary
iKc'usion while on thiouracil therapy; in a former study/® one of ten patients did
h i\e coronary occlusion. Therefore, there is a real possibility of actually harm-
ing a cardiac patient by lowering the metabolic rate even though the pain rray be
relieved.

Aside from these considerations, is the patient able to do more work after
thenipy.^ W’e found, as others have,*'® that the optimum effect in regard to
e.xercise tolerance and tvell-being in general is obtained at a basal metabolic
level ranging from -10 to -20. Above this level the patients have loo much
anginal pain; below, they are too dull mentall}'^ and are apt to have intermittent
claudication, as occurred in two of our patients. Even at the optimum level
ihe'ir ability to do work is not great and is sharplj^ limited b}' a low myocardial
reset \e. I'he limiting factor to exercise simply changes from anginal pain to
dyspnea or to a general tired feeling. Only one of our patients was able to
resume light Avork. Certainly if a patient has anginal pain when his basal meta-
bolism normally is -10 it would be foolhard}’^ to attempt to improve his condi-
tion by further lowering his metabolism.

SUMMARY AND CONCLUSIONS

Thiouracil was administered to eight nonhypertensive cardiac patients with
various degrees of anginal pain. All of them had normally functioning thyroid
glands, except one wdio may have had masked hyperthyroidism. Six of these
patients had previous coronary occlusion. The seventh had definite electro-
cardiographic changes indicative of coronary disease after exercise, and the eighth
had rheumatic heart disease with severe aortic insufficiency and bundle branch
block.

The relationship betAveen the level of metabolic rate, the degree of pre-
cordial pain, and exercise tolerance A\'as folIoAA'ed in each patient. In four of the
patients, therapy Avas stopped after periods ranging from three AA'eeks to tAAm
months for the folloAving reasons; toxic skin rashes in tAA'O instances, onset of
.^CA'ere exertional and nocturnal dyspnea, and failure to loAA'^er the basal metabolic
rate Avith the dosage used. No real benefit on either precordia! pain or exercise
tolerance aams experienced by any of these four patients.

The four remaining patients AA'ere treated and folIoAved for OA^er a year-
In two of them it AA-as possible to attain myxedema levels. In general, precordial
pain AA'as beneficially affected, at least for a period of time, in each of these
patients; at certain times exercise tolerance AA'as doubled and e\'en quadrupled.
HoAvever, all of them except one lost his increased ability to do AA'Ork at the end
of the one-year period. One patient had symptoms resembling coronary occlu-
sion during the course of therapy.

DI PALMA AND MA GOVERN ; DISADVANTAGES OF THIOUILVCIL ^503

The disadvantages of thiouracil as a drug for use in patients with normally
functioning thyroid glands may be listed as follows: toxicity of the drug, neces-
sity for close supervision of the patient over long periods of time, inability to lower
metabolism when the basal metabolism is low to start with, tendency toward
vyater retention, particularly deleterious in cardiac patients, and necessity for
continual therapy in order to maintain results.

. Thiouracil therapy for angina pectoris is therefore not recommended as a
routine procedure. It is indicated in angina pectoris, when the basal metabolic
rate is elevated, and can be used as a therapeutic test by those who wish to select
patients with angina pectoris for thyroidectomy.

REFERENCES

1. Blumgart, H. L., Levine, S. A., and Berlin, D. D.: Congestive Heart Failure and Angina

Pectoris: The Therapeutic Effect of Thyroidectomy on Patients Without Clinical or
Pathological Evidence of Thyroid Toxicity, Arch. Int. Med. 51; 866, 1933.

2. Blumgart, H. L., Berlin, D. D., Davis, D., Riseman, J. E. F., and Weinstein, A. A.: Total

Ablation of the Thyroid in Angina Pectoris and Congestive Failure, XI. Summary
of Results in Treating Seventv-Five Patients During the Past Eighteen Months. J. A.
M. A. 104; 17, 1935.

3. Clark, R. J., Means, J. H., and Sprague, H. B.: Total Thyroidectomy for Heart Disease.

Experience With Twenty-one Patients at the Massachusetts General Hospital, New
England J. Med. 214; 277, 1936.

4. Cutler, E. C., and Schnitker, M. T.: Total Thvroidectomv for .Angina Pectoris, -Ann. Surg.

100: 578, 1934.

5. Friedman, H. F., and Blumgart, H. L.: Treatment of Chronic Heart Disease by Lowering

Metabolic Rate. The Necessitv for Total .Ablation of the Thyroid, J. A. M. A. 102;
17, 1934.

6 Claiborne, T. S., and Hurxthal, L. M.: Results of Total Thvroidectomy in Heart Disease.
New England J. Med. 216; 411, 1937.

7. .Astwood, E. B.: Chemotherapy of Hyperthyroidism. The Har\'ey Lectures, Lancaster,

Pa., 1944-1945, Science Press Printing Co.

8. Williams, R. H,, Bissel, G. W., Jandorf, B. J., and Peters, J. B.: Some Metabolic Effects

of Thiouracil With Particular Consideration of .Adrenal Functions, J. Clin. Endocrinol.
4; 58, 1944.

9. Raab, W.: Diminution of Epinephrine Sensitivity of the Normal Heart Through Thio-

uracil, J. Lab. & Clin, Med. 30; 774, 1945.

10. Raab, W.; Thiouracil Treatment of Angina Pectoris, J. A. M. .A. 128; 249, 1945.

11 Stewart, H. J., and Evans, W. F.: Peripheral Blood Flow in Mvxedema, .Arch. Int. Med.
69; 808, 1942.

12. Riseman, J. E. F., Gilligan, D. R., and Blumgart, H. L.: Treatment of Conge.stivc Heart

Failure and Angina Pectoris by Total .Ablation of the Normal Thyroid Gland. XVI.
The .Sensitivity of Man to Epinephrine Injected Intravenoush- Before and .After Total
Thyroidectomy, .Arch. Int. Med. 56; 39, 1935.

13. Stewart, H. J., Deitrick, J. E., and Crane, N. F.: Studies of the Circulation in Patients

Suffering From Spontaneous My.xedema, J. Clin. Inve.stigation 17; 237, 1938.

14. Gibson, J. G., II, and Harris, W. H.: Clinical Studies of the Blood Volume. 11. Hyper-

thyroidism and Myxedema, J. Clin. Investigation 18; 65, 1939.

15. DiPalma, J. R., and Dreyer, N. B.: Failure of Thiourea to .Alter the .Autonomic Respon.ses

of Intact Animals, Endocrinol, 36: 236, 1945.

16. .Astwood, E. B.: Some Observations on the Use of Thiobarbital as an .Antithyroid .Agent

in the Treatment of Graves’ Disease. J. Clin. Endocrinol. 5: 345. 1945.

('AKDIOVASCULAR DEFECTS IN SELECTIVE SERVICE

REGISTRANTS

( '(.f-ONEL Richard H. Eanes, M.C., United States Army, and Kenneth H.
.McGill, A.B., and Mardelle L. Clark, A.B., Washington, D. C.

C '^ARDIO^^ASCULAR defects have consistently ranked among: the five
leading causes for rejection of men liable for military service who were
plu'sicalJy examined through the Selective Service System since 1940. Some
cardiovascular defect was considered the most important cause for rejection
uf one in every fourteen men disqualified for military service at the end of 1944.
In addition, approximately the same ratio of the World War II veterans who were
receiving disability pension awards in the fall of 1944 had cardiovascular defects
as their major disability.

The widespread prevalence of heart defects among men 18 through 44
years of age is not surprising, since heart disease is the leading cause of death
among men between the ages of 25 and 44 and third in importance as a cause of
death among those 15 through 24 years of age. These defects were found in 83
of every thousand registrants examined by Selective Service local board physi-
cians during 1940 and 1941, the peacetime period of Selective Service operation.
Vahmlar heart disease (rheumatic and syphilitic) and arterial hypertension were
the most frequent diagnoses recorded, as well as the leading causes for rejection
of Selectiv^e Service registrants during both peacetime and wartime.

The Armed Forces’ standards for acceptance of registrants with cardio-
vascular defects have undergone only slight changes since 1940.* Differences

From the Medical DivLsIon and tlie Division of Kcsearcli and Statistics, National Headquarters,
.Selectiro Service System.

This report Is based on sample studies of the results of e.xaminations recorded on DSS Form 200,
Reports of Physical E.xaminatlon, for Selective Service registrants physically c.xamined at local boards
during 1940-1911, and DSS Form 221, Reports of Physical Examination and Induction, for registrants
examined at local boards and induction stations during 1942-1944. Cov'erage of the sample studie-s
varied from 10 to 2~> per cent of the e.xaminations. Additional data on cardiovascular defects among
Selective Service registrants are contained in the following bulletins published by National Head-
quarters of the Selective Service System: Folk, O. H., McGill, K. H., and Rowntreo, L. G. : ifedical
Statistics Bulletin No. 1, Analysis of Reports of Physical E.xamination. Nov. 10, 1941; Edwards, T. I.,
McGill, K. H., and Rowntree, L. G.t Medical Statistics Bulletin No. 2, Causes of Rejection and
Incidence of Defects. An Anal.vsis of Reports of Physical E.xamination From 21 Selected States, Aug.
1, 1943; Grove, C. H., AlcGill, IC. H.. and Rowntree, L. G.; Medical Statistics Bulletin No. 3, Physical
Examination of Selective Service Registrants During AVartime. Nov. 1, 1914.

Received for publication Dec. 31, 1945.

♦The cardiovascular standards for acceptability of Selective Service registrants are contained in
War Department Mobilization Regulations 1-9: Standards of Phy.sical E.xamination During Mobi-
lization. In general, the only cardiovascular defects which were acceptable were (a) a pulse rate of
100 or over if not persistent and not duo to paro.xy.smal tachycardia; (b) a pulse rate of .'SO or under which
is provc<l the n.atural rate, or a temporary rate, or duo to drugs; (c) sinus arrhythmia: and (d) temporary
elevation of blood jjre.ssure due to excitement. A pulse rate of 50 boats per minute became unaccept-
able in April. 1944, but the change had little olTcct on the rate of rejection of registrants. No regis-
trants ■with cartUovascular defects were acceptable for limited service.

504

5G5

EANES ET AL. : CARDlOVASCUl.AR DEFECTS

in examining procedures, however, as well a» in application of the cardiovascular
criteria, produced differences botli in the rates of rejection for cardiovascular
defects and in the diagnoses of certain specific defects in the group. During
1940 and 1941, all the registrants receiving physical examination were examined
by local board physicians, who w'ere usually general practitioners. Most of the
rejections during this time occurred at the local board level. The physical stand-
ards were high, and most of the rejections were made on diagnoses of physical
rather than mental defects. The situation was reversed beginning in early 1942,
when physical standards were lower, particularly in reference to dental and visual
defects, and local board physicians rejected only those registrants with the more
serious defects which were manifestly disqualifying. After that, most of the
rejections were made by specialists at the induction stations, where psj-chiatric
examinations, blood pressure readings, and other special tests were given only as
a part of the routine examination at the Armed Forces’ induction stations.

The rates of rejection for cardiovascular defects presented in this discussion
and their relative importance as causes for rejection are based on their occurrence
as the most serious defects for which the registrants were rejected. The tables
showing the prevalence of these defects among all registrants include, in addition
to the principal causes for rejection, disqualifying heart defects which were second-
ary causes for rejection and also the less serious heart defects such as transient
hypertension, arrhythmias, and functional murmurs.

NUMBER CURRENTLY REJECTED

Among the nearly five million registrants who were classified as unfit for
any form of military service as of January 1, 1945, an estimated 300,100, or
6.7 per cent, had been rejected because the principal defect was cardiovascular
(Table I)^ This figure includes not only the registrants in Class 4-F on that
date, but also those who had been rejected for cardio\ ascular defects and later
reclassified in occupationally deferred classes because they were in essential
industry or agriculture. It does not include, however, registrants who had been
rejected for cardiovascular defects who were re-examined at a later date and in-
ducted or were again rejected for a primary cause which was not cardiovascular.

Table I. Estimated Number of Registrants Aged 18 to 37 Years in Rejected Classes
Because of Cardiovascular Defects,* Jan. 1, 1945

An races
Whitef . :
Negro . .

rejected for

Race

! cardiovascular defects
total in

REJECTED i
CLASSES

1

number

percentage of

TOTAL

4.493,000 !

6.7

3,621,000

250,900 1

6.9

872.000

5.6

i

♦Includes registrants in Class 'I-F and also those transferred from Class -l-F to the occupationally
. deferred classes, 2-A (F), 2-15 (F), and 2-C (F),

. tlucludes all races other than Negro.

50G

AMERICAN HEART JOURNAT-

Registrants who were rejected for cardiovascular defects were thefouith
group in order of importance, exceeded only by those rejected for mental disease,
mental deficiency, and musculoskeletal defects. Relatively more tvhite tlian
Negro registrants who were rejected had cardiovascular defects as the principal
cause for their rejection.

The specific diagnosis in more than four of every ten rejections for cardio-
vascular defects was ^•alvular heart disease, most of which was rheumatic in
origin. Arterial hypertension was recorded as the diagnosis in three of every ten
cardio\'ascular rejections.

REJECTION RATES FOR CARDIOt'^ASCUI.AR DEFECTS

The number of registrants rejected for cardiovascular defects decreased
from 44 of every thousand registrants physically examined in 1940 and 1941 to
35 per thousand examined in 1944 (Table II). A'luch of the decrease was the
result of the changes in examining procedure discussed previously , which gave
an increased value to and a resulting increase in the rate of rejection for neuropsj'^-
chiatric defects. Other factors, which also effected a decrease in rejection rates
for all defects combined, were: (1) changes in the age composition of the group
which was subject to induction into the Armed Forces; (2) lower standards for
acceptance, particularly those pertaining to dental and visual defects and educa-
tional deficiency, during wartime; (3) a Presidential order at the end of 1942, pro-
hibiting the direct enlistment of men 18 through 37 years of age at Armed P'orces’
recruiting stations.* This cessation of voluntary enlistments made available for
examination through Selective Service a large number of physically fit registrants
who would not otherwise have been represented in Selective Service data.

Table II. Estimated Rejection Rates for Cardiovascular Defects, by

Race, 1940 - 1944 *

i

year

1

ALL KACKS

WHITEf

NEGRO

1940-1941

43.6

44.1

39.6

1942

35.0

33.8

42.5

1943 i

29.1

27.3

38.6

1944

34.7

33.4

43.5

*Rate per 1,000 examined.
tlnclucUs ail races other than Nesro.

Among white registrants, the rates of rejection for cardiovascular defects
decreased from 44 of each thousand examined in 1940 and 1941 to 33 per thousand
examined in 1944. On the other hand, Negro cardiovascular rejection rates
tended to increase during wartime, when the majority were examined at induction

♦DurlnK 19J0-1011, the ago.s of men dcsignatcfl as- lialdc for military sendee were 21 through .10
ypan?: (luring 1942, they M*ero 20 through 44 years; and in <?ie two succeeding yeatf*'. registrants IS through
^7 years were liable, with increasing (^mphasis during 1044 on the Induction of men under go years of
age. * '

_ EANESETAL.: CARDIOVASCULAR DEFECTS 507

stations where routine blood pressure readings were made. This is borne out by
the fact that hypertension was responsible for almost one-half the Negro cardio-
vascular rejections during the first two wartime years.

SPECIFIC DIAGNOSTIC GROUPS OF CARDIOVASCULAR DEFECTS

Although cardiovascular defects were recorded on the physical examination
reports of 83 registrants in every thousand examined by local board physicians
during 1940 and 1941 (Table III), they were the most important causes for rejec-
tion of only 44 per thousand examined. They were noted either as secondary
causes for rejection or as minor or functional defects in the remaining 39 cases
per thousand. The more serious defects, such as vahmlar heart disease, were
almost invariably cause for rejection, so their rates of prevalence and rejection
were approximately equal. On the other hand, arrhythmias, functional murmurs,
and tachycardia were more important among the total number of physically
examined registrants than among those rejected.

’ Table III. Prevalence of Cardiovascular Defects and Percentage Distribution of
Rejections for These Defects Among Registrants Physically
Examined at Loc.^l Boards, 1940-1941*

MAJOR SUBGROUP

PREVALENCE PER 1,000
EXAMINED

PERCENTAGE DISTRIBUTION

OF REJECTIONS

1

ALL RACES

WHITEf

NEGRO

.ALL RACES

AVHlTEt

NEGRO

Total cardiotmscular . . . .

83.1

84.6

71.8

100.0

100.0

100.0

Rheumatic and valvular.

28.4

28.5

26.0

i 44. 1

44,6 !

40.0

Hypertension, arterial. . .

16.6

16.3

19.1

i 31.6

30.6 1

40.0

Tachycardia, persistent . .

6. 7

7.2

3.0

1 8.4

8.8

5.0

Cardiac hypertrophy. . . .

2.8

\ 2.8

3.0

2.5

2.5

2.5

Cardiac arrhythmia

Cardiovascular diseases.

0. .1

1 5.8

3.8

t 1.8

1.8

1.3

■ otherf

4.1

4.3

2.8

6.5

6.7

5.0

Functional murmurs. . . .
Other cardiovascular de-

5.0

1 5.2

1

4.3

0.6

1

0.6

1

0.5

' fects §

14.0

14.5

9.8

4.5 !

!

4.4 !

1

5.7

^Corresponding data for induction stations are not availaide for the period 1940-1941.

tincludes all races other than Negro.

tincludes diseases of the heart and vascular system in which the. physician recorded a diagnosis
other than rheumatic heart disease, valvular heart disease, hypertension, hypertrophy, tachycardia,
or arrhythmia.

fincludes entries describing signs, symptoms, or diseases of the heart and circulatory system not
elsewhere classinable. such as; bradycardia, artcrio.sclerosis, arterial hypotension, and hypertension or
tachycardia described as nervous or functional in type.

Valvular heart disease was the most frequently recorded cardiovascular
defect: It occurred in 28 of every thousand registrants examined during peace-
time. Rheumatic fever was specified as the etiologr- in only 4 per thou.sand of

SOS

AMERICAN' HEART JOURNAL

these cases.* The valvular heart disease category also included diagnoses of
defects of specified valves and systolic murmurs unspecified as to t 3 ^pe. These
unspecified sj'stolic murmurs accounted for almost 10 per cent of all the cardio-
^•ascular defects recorded. In 79 per cent of the cases where the valve was
■specified (excluding definite rheumatic heart disease) the mitral valve was affected,
in 14 per cent the aortic valve was affected, and in 4 per cent both the aortic and
the mitral valves were affected. Endocarditis, which is frequently preceded or
.'iccompanied bj'- rheumatic involvement, was recorded for less than one registrant
in (ivery thousand examined.

The prevalence rate of such cardiovascular defects as h^'^pertension, tachj’’-
cardia, cardiac arrhythmias, murmurs, and hypertrophy^ is slightly understated,
for the reason that they?^ were often recorded as observations on which a specific
diagnosis of organic heart disease was based. In these cases, the more serious
diagnosis was counted. Hy^pertension was recorded as the chief diagnosis in
approximately 20 cases per thousand, 3 per thousand of which were regarded as
transient in ty'^pe. Tachy'^cardia was third in relative frequency among the cardio-
\'ascular defects recorded, but it was noted as the most important diagnosis for
13 registrants in every^ thousand examined and was specified as functional tachy’-
cardia in nearly one-half of these cases. The functional type of tachycardia,
as well as transient hypertension, is included in the miscellaneous group of cardio-
A’ascular defects shown in Table III.

Cardiovascular defects were noted more often for white than for Negro
registrants. Of the specific defects, the valvular heart disease group was almost
equally important in the two races. Cases diagnosed as being rheumatic in
origin, however, occurred almost three times as often among the white registrants
as they' did among Negroes.

Of all the registrants who were rejected for cardiovascular defects during
peacetime, almost one-half had valvular heart disease. Approximately 3 in 10
had hypertension as the principal cause for rejection. No other single defect
approached this relative importance among cardiovascular rejections, the nearest
being tachy'cardia, which accounted for about one in 12 of the cardiovascular
rejections.

The importance of the various cardiovascular defects as causes for rejection
of white registrants was similar to that of all races. Among Negroes, however,
hypertension assumed first place, accounting for 4 in every 10 Negro cardio-
vascular rejections.

The changes in e.xamining procedure which began in 1942 resulted in impor-
tant changes in the diagnoses of specific cardiovascular defects. The first of
these, resulting from the routine psy'chiatric examination at induction stations,
produced a shifting of diagnoses from the cardiovascular to the psychiatric
category'. Thus, conditions which during peacetime were recorded by local board
physicians simply' as tachycardia were diagnosed by' psy’chiatrists as paroxy'smal

‘Acute rheumatic fever «as found infrequently araoiiK Selective Service registrants, since men witli
lids condition .seidom came up for physical evamination until the acute .>:lage had subsided. It t^as
diaimosed in 0.1 per tltousand registrants examined during 1940 and 1941, probably through afOdavits
from the registrants' personal physicians.

EANESETAL.; CARDIOVASCULAR DEFECTS 509

tachycardia or neurocirculatory asthenia. The prevalence of tachycardia (in-
cluding functional) decreased by almost one-third under this procedure, while
that of paroxysmal tachycardia and neurocirculator^'^ asthenia tripled between
1940 and 1944.

The second change, occasioned b}^ the routine blood pressure readings at
induction stations, affected the relative importance of the specific defects within
the cardiovascular group. As hypertension was diagnosed more frequently,
it increased both in recorded prevalence and in importance as a principal cause
for rejection, and there was a corresponding decrease in most of the other specific
defects.

A third factor which affected the prevalence date for cardiovascular defects
in wartime was that fewer minor heart disturbances appeared in the physician’s
summary of defects from which the wartime figures were obtained. This largely
accounted for the decrease in recording of all heart defects from the peacetime
figure of 83 to the wartime figure of 51 per 1,000 examined.^ The relative impor-
tance of the more serious defects, however, was approximately the same as during
peacetime.

Hypertension and valvular heart disease were the defects most frequently
found, the former in 18.4 cases per thousand examined and the latter in 16.5
(Table IV). Tachycardia, next in frequency, was tabulated in only 4.5 cases per
thousand.

Cardiovascular defects occurred in 50 of every thousand white registrants
examined and in 58 per thousand Negroes. This higher rate of prevalence among
the Negroes reflects the more frequent diagnoses of hypertension for that race.

Table IV. Prevalence of Cardiovasccla.r Defects and Percentage Distribution of
Rejections for These Defects Among Registrants Physically Examined at Local
Boards and Induction Stations, 1942-1943

MAJOR SUBGROUP

PREVALENCE PER 1,000
examined

j

PERCENTAGE DISTRIBUTION

OF REJECTIONS

all races

WHITE*

NEGRO ■

ALL RACES

WHITE* 1

NEGRO

Total cardiovascular

51.0

49.8

57.7

100.0

100.0

100.0

Rheumatic and valvular

16.5

16.6

16.2

44.7

46.6

36.5

Hypertension, arterial

18.4

16.7

1 27.5

35.5

32.8

47.3

Tachycardia, persistent

4.5

4.8

! 2.7

6. 1

6.7

3 5

Cardiac hvpertrophy

1.8

1.7

2.7

3.6

3..^

4.5

Cardiac arrhythmia

0.6

0.6

0.5

0.3

0 4

0.3

Cardiovascular diseases, otherf . . .

2.4

2.4

2.3

5.9

6 3 1

4.2

Functional murmurs

3.6

3.8

2.8

0.3 1

0.3 i

0.2'

Other cardiovascular defectsf

3.2 i

3.2 i

1

3.0

3.6 ’

3.6

1

3.5

*Inclu(lcs all races other than Negro.

tIncUides diseases of the heart and ^-asciilar system in which the physician recorded a diagnosis
other than rheumatic heart disease, valvular heart disease, hypertension, hypertrophy, tachycardia, or
■ arrhythmia.

tlncludcs entries describing signs, symptoms, or diseases of the licarl and circulatory system not
elsewhere classlflblc, such as; bradycardia, arteriosclerosis, arterial hypotension, and hypertension or
tacliycardia dascribed as nervous or functional in typo.

.-,10

AMERICAN HEART JOURNAL

Cardiac hypertrophy was the only other cardiovascular defect recorded more
frequenth for Negro than for white registrants.

As in peacetime, the most important causes for rejection were the valvular
heart disease group and arterial hypertension. These ttvo defects accounted for
.SO per cent of the wartime cardiovascular rejections. The two defects combined
were less important for white registrants than for Negroes, but the diagnosis of
\aivular heart disease was far more important among the white race and that of
hypertension w'as more important among the Negroes. Tachycardia accounted
for relatively one-half as m.any Negro as white rejections for cardiovascular
defects.

CARDIOVASCULAR SYPHILIS AND VARICOSE VEINS

Cardiovascular defects described as due to syphilis have been included in
the syphilis categorj'- rather than under cardiovascular defects in Selective .Service
data. However, the pre\aience of cardiovascular defects in which syphilis was
specified as the etiologj'^ was low during both the peacetime and the wartime
periods. The incidence was 0.3 per thousand registrants examined for all races,
0.1 for w'hites, and 1.7 for Negroes. It accounted for only 0.1 per cent of the
rejections during each period.

Varicose veins were noted in 32 registrants of every thousand examined
during 1940 and 1941, but during wartime they Avere included in the summary
by induction station examiners in only 16 cases per thousand. They were re-
sponsible for little more than 1 per cent of the rejections.

CARDIOVASCULAR REJECTIONS IN RELATION TO AGE

Rejection rates for cardiovascular defects increased with increasing age.
The relative importance of specific diagnoses as cau.ses for rejection, however,
differed in the various age groups. This is illustrated in Table V, which indicates
the relative importance of the three leading cardiovascular diagnoses among regis-
trants rejected in 1944.

Hypertension and valvular heart disease were almost equally important
among all registrants rejected for cardiovascular defects; each accounted for
more than 4 in every 10 of these rejections. Tachycardia accounted for less than
one in 10 cardiovascular rejections.

A reA iew of the percentages of rejections for the specific defects in the various
age groups shows that hypertension increased sharply with increasing age*
that \aJvular heart disease was Jess than one-half as important among men 30
years of age and over as among the 18-year-old registrants; and that the propor-
tion rejected for tachycardia was relatively constant in each age group.-

Hypertension was the only cardiovascular subgroup of less relative impor-
tance as cause for rejection of Avhite registrants than of all races; for Negroes,-
it was the only defect more important for them than for all races. It accounted
for 40 per cent of the white as compared to 67 per cent of the Negro cardiovascular
rejections.

EANES ET AL. : CARDIOVASCULAR DEFECTS 51,1

. Table V. Percentage of Cardiovascular Rejections Du

Diagnoses, by Age and Race*

E TO Specific

PERCENTAGE OF CARDIOVASCULAR REJECTIONS FOR

AGE (yR.)

TOTAL

ARTERIAL

RHEUMATIC AND
VALVULAR HEART

TACHY-

OTHER

hypertension

DISEASE

CARDIA

All ages

100.0

Aj/ Races

43.7

42.4

6.7

!

7.2

18...

100.0

14.0

69.4

6.1

10.5

18-25.

100.0

35.5

49.2

8.0

7.3

26-29.

100.0

44.1

43.7

6.3

5.9

30 and over

100.0

52.7

33 .-8

6.4

7.1 .•

All ages.

100.0

Whitet

38.9

45. 7

7. 7

7. 7

.18 ;....;

100.0

9.5

72.7

6.5

11.3

19-25.....;...

100.0

28.9

54.4

9.0

777

26-29.

100.0

38.8

47.6

7.4

6.2

30 arid over

100.0

48.8

36.4

7.3

7.5

All ages

100.0

Negro

67.0 ;

26.0

2 2

4.8

18......;

100,0

39.8 i

51.1

3.4

5.7 '

19-25:.

100.0

61.8 j

29.0

3.8 .

5.4

26-29.

100.0

67.5 j

26.6

1.5

4.4

30 and over. . ;

100.0

74,8 j

I

19.4

1.3

4.5

*Basecl on a sample of Reports of Physical Examination and Induction for registrants intiucted or
‘ rejected during February, 1944, through May, 1944.

‘ ffncludes all race.s other than Negro.

In general, the distribution of the various cardiovascular defects as causes
for rejection in each racial category followed the same trends as for all races.
Hypertension increased in relative importance with increasing age; valvular
heart disease decreased sharply as age increased, and tachycardia decreased only
slightly.

/ OCCUPATIONS OF CARDIOVASCULAR REJECTEES

The occupational distribution of registrants rejected because of cardio-
vascular defects is shown in Table VL Selective Service policies regarding
occupational deferments affect the representativeness of certain of these major
occupational groups, however, notably the farm owners and farm laborers.
Their physical and mental defects are probably less representative of the farmers
in the general population than of those in other occupations, since the Tydings
Amendment to the Selective Training and Ser\nce Act late in 1942 resulted in
widespread occupational deferments in the agricultural groups, without physical
e.xamination.

512

AMERICAN HEART JOURNAL

T\ble VI. Percentage of Rejections in M.ajor Occupational Groups
Based on Cardiovascular Defects*

I

occupation

PERCENTAGE OF REJECTIONS IN
EACH OCCUPATION GROUP DUE

TO CARDIOVASCULAR DEFECTS

ALL RACES

1

t

white!

NEGRO

9.2

9 2

9 3

12 1

12.1

6 9

+

6 9

6.8

!

t

12.3

12 7

12.7 1

114

PIf*f!rpl nnH UinHrfiH

115

9 9

Q R

9 5

9 2 1

11.6

10 5

10.5

6 4

t

9.9

Laborers, except farm

7 9

15 1

14 8

t

3.9

Emergency workers and unemployed

4 7 i

5 0

Nonclassifiable and not stated

7.2

1

7.2

7.2

*UasDd on a sample of Reports of Physical Examination anti Induction for registrants examined
during February, 1944, through April, 1944.
tincludes all races other than Negro.

JNegro rates not presented for occupations with less tb.m 2 per cent of total Negro rejections.

Cardiovascular defects accounted for 9 per cent of the rejections in all occupa-
tions, with approximately the same proportions of white and Negro rejections
made for these defects. Only three occupational groups, the farm owners and
laborers, other laborers, and the emergency workers and unemployed, had rela-
tively fewer cardiovascular rejections than the average for all occupations.

Students had the highest proportion of rejections for cardiovascular defects.
These were the principal defects of almost one in every 6 of the student rejections-
Approximate!}^ one in every 8 rejections in the professional group and in the
managerial and official group were made because of cardiovascular defects.
Among emergency workers and the unemployed, at the lowest extreme, only
one in 20 was rejected for cardiovascular defects.

Among white registrants, cardiovascular rejections in each occupational
group were similar to those for all registrants. Relatively more Negro than ivhite
registrants who were craftsmen and foremen, operatives, and laborers were re-
jected for cardiovascular defects.

RE-EXAMINATION OF REGISTRANTS WITH CARDIOVASCULAR DEFECTS

Early in Selective Service e.xperience the question arose as to whether any
considerable number of men who had been found disqualified for military service
might have been rejected on mistaken diagnoses. In order to determine the
probable amount of salvage of such men, and also to make possible a detailed
analysis of current problems in cardiovascular diagnosis, a re-examination
study was made by special medical advisory boards in five of the largest cities in

eanesetal.: cardiovascular defects 513

the country. This study, covering re-examination of 4,994 men formerly rejected
because of cardiovascular defects and neurocirculatory asthenia, was conducted .
by members of the Subcommittee on Cardiovascular Diseases, National Research
Council, who were appointed as members of special Selective Service Medical
Advisory Boards.^ .

Of the 4,994 men who were re-examined, 17.3 per cent were resubmitted as
qualified for general military service, while the remaining 82.7 per cent were
retained in the rejected classification. In view of the relatively small percentage
of registrants reclassified for induction, the time required for re-examination,
and the scarcity of expert examiners during wartime, the wisdom of extending
the re-examination of registrants rejected for cardiovascular defects was considered
doubtful.

The five leading causes for rejection, in order of their importance, were:
rheumatic heart disease, found on first e.xamination in 50 per cent of the total
4,994, and diagnosed for 59.9 per cent of those rejected after re-examination;
arterial hypertension; neurocirculatory asthenia; sinus tachycardia; and con-
genital heart disease.

Several problems in diagnosis raised by the study were posed for further
research, possibly in a follow-up of the borderline cases. Chief among these
were questions of (1) interpretation and significance of apical systolic murmurs;
(2) the possible need for extending the upper limits of blood pressure standards
in very nervous young men to 160 mm. or slightly higher, provided Ihe diastolic
pressure does not exceed 90 mm.; extending the limits of pulse rates at rest to
approximately 40 to 120 per minute; and expanding the limits on heart size. The
usefulness of exercise tests in cardiovascular e.xamination for military service was
also questioned.

SUMMARY

Some of the more important facts derived from Selective Service experience
in the physical e.xamination of men with cardiovascular defects may be sum-
marized as follows:

1. Cardiovascular defects are among the leading causes for rejection of
Selective Service registrants. Among men in the rejected classes, they are the
fourth group in order of importance, e.xceeded only by mental disease, mental
deficiency, and musculoskeletal defects.

2. More than 300,000 registrants, or 6.7 per cent of the total in the rejected
classes on Jan. 1, 1945, had heart defects as the most serious defect. The per-
centage of white registrants with these defects was larger than that of Negroes.

3. Valvular heart disease (rheumatic and syphilitic) and arterial hyper-
tension have been the leading specific causes for cardiovascular rejection, as well
as the most frequently recorded cardiovascular defects, during both peacetime
and wartime. Valvular heart disease occurred more frequently among white
registrants, while hypertension was a much more important diagnosis among the
Negroes.

AMERICAN HEART JOURNAL

51 i

4. Within the various age groups, rejections for rheumatic-valvular heart
disease decreased as age increased; it was particularly important among 18-
year-old registrants, accounting for nearly 70 per cent of their cardio\Tiscular
rejections during a four-month period in 1944.

5. Arterial hypertension became more important as a cause for rejection
with increasing age. Among registrants 30 years old and over who were rejected
because of cardiovascular defects it accounted for more than one-half the rejec-
tions. Less than one-half the white rejections 30 years of age and over were made
for this cause, however, ivhile three-fourths of the Negroes in this age group who
were rejected for cardiovascular defects had arterial hypertension.

6. Emergency workers, the unemployed, and farmers had the lowest per-
centages of rejections for cardiovascular defects; students had the highest per-
centage of rejections for these defects.

REFERENCES

1. Edwards, T. I., and Heilman, L. P.: Methods Used in Processing Data From the Physical
Examination Reports of the Selective Service System, J. Am. Statistical Association 39:
165, 1944.

2. Rowntree, L. G., McGill, K. H., and Edvrards, T. I.; Causes of Rejection and Incidence of
Defects Among 18 and 19 Year Old Registrants, J. A. M. A. 123: 181, 1943.

3. a. Levy, R. L., Stroud, W. D., and White, _P. D.: Report of Re-examination of 4,994 Men

Disqualified for General Military' Service Because of the Diagnosis of Cardiovascular
Defects, J. A. M. A. 123: 937, 1943; ibid., 123: 1,029, 1943.
b. Fenn, G. K., Kerr, W. J., Levy, R. D., Stroud, W. D., and White, P. D,; Re-examina-
tion of 4,994 Men Rejected for General Military Service Because of the Diagnosis of
Cardiovascular Defects, Am. Heart J. 27; 435, 1944.

Clinical Reports

ACUTE PERICARDITIS SIMULATING CORONARY
ARTERY OCCLUSION

Captain Charles W. Coffen, M.C., and Major Maxwell Scarf, M.C.

; Army of the United States

A CUTE pericarditis of infectious origin may present various clinical patterns.

Its existence is often undetected because the symptoms and signs are
weighed with those of the underlying disease. Occasionally, its onset is mani-
fested by severe precordial pain and shock, simulating an acute coronary occlu-
sion. Cases of this type have been described by Barnes and Burchell.* Differ-
entiation between the two conditions is, of course, important because of the differ-
ence in their management and prognosis. In a recent small series of cases of
acute pericarditis simulating coronary occlusion which were reported by Wolff
mention was made of the presence of a slow pulse as a differentiating feature
of pericarditis. Recently we saw a patient with severe precordial pain, shock,,
and slow pulse in whom myocardial infarction was suspected but in whom further
study led to a diagnosis of acute pericarditis. The case is presented bec.iuse this
particular clinical picture is not well known.

CASE report

A 26-year-old Army officer came to the hospital at 8 A.M. on Oct . 5, 1944, with the presenting
symptom of intense .substernal pain which had awakened him three hours earlier. • The pain
radiated to both shoulders, was aggravated by breathing, and prevented him from assuming a
•recumbent position. He had previously been in good health and there was no history suggesting
that he had ever had rheumatic .fever, tuberculosis, coronary insufficiency, trauma to the chest,
or a recent respiratory infection.

Preliminary e-xamination revealed a young man who did not appear ill e.xcept that ho was
unable to lie flat on the examining table because of pain in the anterior midchest. No abnormality
of the heart, lungs, or thoracic wall could be detected. The blood pressure was 120/80 and the
heart rate, 72 per minute. During the examination a sudden and dramatic change occurred in
the appearance of the patient. The face became ashen and the lips cyanotic. The heart rate
.fell to 38 per minute, the rhythm became irregular, and the sounds almost inaudible. The
blood pressure could not be measured. The skin became covered with a cold, drenching sweat.
This alarming situation improved gradually after the administration of morphine sulfate. The
pulse slowlv increased to 60 per minute and the blood pressure to 90/60. The patient was trans-
ferred to a hospital bed where he was placed in a sitting position and in an oxygen lent- Two
more doses of morphine were necessary to control the pain which remained severe until noon.
Six hours after admission the patient was completely free of pain and could lie flat without dis-

Rcccived for puWicatiou Oct. 25. 1945.

.515

510

AMERICAN HEART JOURNAL

comfort and without the use of oxygen. He presented a normal appearance. The heart sounds
%vere clearer, the rate was 80 per minute, the rhythm was regular, and the blood pressure was
120/80. This respite, however, was brief, and a few hours later cyanosis reappeared, the heart
rate increased to 130 per minute, and the temperature rose to 100° Fahrenheit. Fortunately
resumption of o-xj'gen therapy was followed by an amelioration of symptoms after several hours.
The following morning the temperature, pulse rate, and blood pressure reached normal levels
where they remained for the duration of the patient's hospital stay. At this time a pericardial
friction rub became audible over the lower sternum. The friction rub disappeared in several
hours and made its final appearance the following day for a short time. The further course of
the patient was uneventful. No evidence of pericardial effusion or cardiac enlargement was ob-
served. The patient was kept in bed for four weeks and returned to his usual duties after a short
convalescent leave.

The leucocyte count was 16,700 on the day of admission, 12,150 on the following day, and
subsequently normal. The blood sedimentation rate by the Westergren method was 64 mm.
in one hour and did not approach normal limits until the twelfth hospital daj'. The most import-
ant laboratory findings were revealed by the electrocardiograms. As will be seen in Fig. 1, A,
the S-T segments are slightly elevated in Leads I and II without reciprocal S-Tj deviation. Small

A. B. a D. E.

FIk. 1. — The clcctrocarfliograms consist of the three standard limb Ic.ids and Lead CR 4 . The find-
ings are discussed in the taxi. A, Taken Oct. 5, 1944; B, Oct. 0, 1044; C, Oct. 9, 1944; D, Oct. 13, 1944;
E, March 3. ini.S.

Q: and Qj waves are present. In Fig. 1, B, elevated S-T segments are present in all limb leads
and the T waves in all leads are of lower amplitude. Lead CF 4 is normal. C and D of Fig. 1
are representative of subsequent electrocardiograms and show no changes characteristic of myo-
cardial infarction, the only abnormality present being S-T segment elevation in the indirect leads.

Spontaneous mediastinal emphysema or pneumothorax as a cause of the clinical picture’
and electrocardiographic changes'* were precluded by the normal roentgoenograms of the chest
and the absence of reiev'ant clinical findings.

Approximately six months after the onset of the illness, the patient appeared for a routine
examination. He had been asymptomatic throughout this period of time. Physical examina-
tion of the heart revealed no abnormalities. Roentgen examination of the heart was likewise
normal. An electrocardiogram taken at this time (Fig. 1, E) showed that slight elevation of the
S-T segments in Leads II and III was still present.

517

COFFEN AND scarf; ACUTE PERICARDITIS

COMMENT

: At the time the patient had severe substernal pain, shock, and cyanosis,
he appeared critically ill. It is natural to associate this picture with an acute
myocardial infarction. Criteria favoring a diagnosis of acute pericarditis, how-
ever, were present and included the youth of the patient. A significant charac-
teristic of the pain was its aggravation by breathing and change of position.
This rarely occurs in infarction of the myocardium. The slow pulse rate men-
tioned by Wolffs was also present. The transitory friction rub and fever were
more suggestive of myocardial infarction than pericarditis because in the latter
condition these signs tend to be present from the onset and are more persistent.
Finally, the electrocardiographic changes were characteristic of acute peri-
cardities.^

Collapse with slow pulse and low blood pressure may have been the result
of increased vagal tone caused by the pericarditis or by the pleuritis which is
frequently associated with it. A similar reflex vagal stimulation is occasionally
observed following puncture of the chest wall (so-called pleural shock) or during
abdominal operations.

The presence of fever, leucocy,tosis, and an elevated blood sedimentation
rate was considered evidence for an infectious origin of the pericarditis. No
specific etiologic factor, however, was present. Rheumatic fever, tuberculosis,
septicemia, uremia, and disseminated lupus erythematosus are usually revealed
by clinical characteristics not present in the case described. Barnes and Burchelfl
have observed young adults with a benign and apparently limited form of peri-
carditis possibly caused by tuberculosis. Acute pericarditis may be associated
with infections of the upper respiratory tract® and sinuses® and may compliaite
primary atypical pneumonia.^ It has also been described following operative
procedures®’® and in epidemic form.^® In one series of cases, ^ evidence of an upper
respiratory, tract infection was found in 57 per cent of patients. In the remaining
43 per cent, as in our case, no causative agent was demonstrated.

CONCLUSION

A case report of acute pericarditis of unknown etiology is presented to illus-
trate that the clinical picture may be one of intense precordial pain associated
w'ith shock and a strikingly slow pulse. Vagal stimulation of reflex nature from
the inflamed pericardium is suggested as the cause of the collapse and slow
pulse. Acute pericarditis may closely simulate acute coronary occlusion.

518

AMERICAN HEART JOURNAL

REFERENCES

/

1. Barnes. A. R., and Burchell, H. B.: Acute Pericarditis Simulating Acute Coronary Occlu-

sion: A Report of Fourteen Cases, Axi. Heart J. 23: 247, 1942.

2. Wolff, L.: Acute Pericarditis Simulating Mvocardial Infarction, New England J. Med.

2.30: 422, 1944.

3. (a) Scott, A. M.: The Significance of the Anginal Syndrome in .Acute Spontaneous Pneu-

monediastinum. Lancet 1: 13, 1937.

(b) Hamman. L.: Spontaneous Mediastinal Emphysema (Henry Sewall Lecture), Bull.
Johns Hopkins Hosp. 64: 1, 1939.

(r) Hamman, L.: Mediastinal Emphysema, J. .A. M. A. 128: 1, 1945.

4. Miller, H.: Spontaneous Mediastinal Emphysema With Pneumothorax Simulating Organic

Heart Disease, .Am. J. M. Sc. 209: 211, 1945.

5. Willius, F. -A.: Clinic on .Acute Serofibrinous Pericarditis Secondary to .Acute Pharyngitis:

Comment; Treatment; Course, Proc. Staff Meet., Mayo Clin. 9: 637, 1934.

6. Comer, M. C.: .Acute Pericarditis With Effusion: .A Sequel to Sinusitis, Southwestern

Med. 11; 310, 1927.

7. Finklestein, D., and Klaincr, M. J.; Pericarditis .Associated With Primary .Atypical Pneu-

monia, .A.m. Heart J. 28; 385, 1944.

8. Butsch, W. L.: .Acute Pericarditis as Po.stoperative Complication, Proc. Staff Meet., Mavo

Clin. 12; 737, 1937.

9. Spear, P. W.: Fibrinous Pericarditis Following Thyroidectomy, South. M. f. 31: 215.

1938.

10. Bing. H- T.: Epidemic Pericarditis, .Acta med. Scandinav. 80: 29, 1933.

BILATERAL PULMONARY INFARCTION AND PNEUMOTHORAX
COMPLICATING HYPERTENSIVE, CORONARY HEART
DISEASE WITH MYOCARDIAL INFARCTION:

REPORT OF A CASE

H. Milton Rogers, M.D.

- St. Petersburg, Fla.

S pontaneous pneumothorax has been reported in association with a num-
ber of>: clinical conditions, including tuberculosis, pneumonia, and bronchial
asthma, and. secondary to mediastinal emphysema. Marks^ has observed pneu-
mothorax secondary to pulmonary infarction. According to Hamman,^ spon-
taneous pneumothorax may be produced by any of four mechanisms: (1) rupture
of subpleural blebs, (2) a rent in the pleura due to pull of adhesions, (v3) rupture
into the pleura of congenital pulmonary cysts, or (4) mediastinal emphysema
with rupture of the mediastinal pleura. He expressed the opinion that, when
bilateral spontaneous pneumothorax is present, mediastinal emphysema must
precede the pneumothorax.®

It is the purpose of this paper to report a case of bilateral spontaneous pneu-
mothorax associated with pulmonary infarction and myocardial infarction.
Other features of clinical interest in the case^ were the marked increase of the
diastolic blood pressure after renal infarction and the absence of further intra-
cardiac or peripheral manifestations of vascular thrombosis after the institution of
dicumarol.

report of a case

The patient was a white man, 44 years of age, e.xamined first Dec. 14, 1944. He complained
chiefly of dyspnea and cough. He stated that four weeks prcviouslj' he had been seized with severe
substernal thoracic pain, which extended to the left shoulder and elbow. Morphine was neces-
sary for relief. Part-time rest in bed had been instituted for two weeks. .Although dyspnea and
cough had made their appearance, he then had been permitted to resume light activity. This
had been accompanied by increased shortness of breath and hemoptysis. The twenty-four
hours prior to the first examination had been spent on the train, with symptoms increasing in
intensity. Nausea and vomiting were present also.

The past history revealed h 3 'pertension of ten to twelve years’ duration. The blood pressure
had ranged from 200/100 to 210/110. There was no historv’ of rheumatic fever, scarlet fever,

, chorea, or recurrent sore throats.

The results of physical examination revealed a severeh* djspneic, cyanotic, acutely ill white
man. The pulse rate was 140 beats per minute; the blood pressure was 150/100; the temperature
was 100.2° Fahrenheit. There were restricted expansion and posterior dullness to percussion
of the right portion of the thorax. Rdles were present over the right portion of the thorax an-
teriorlj' and posteriorb*. A protodiastolic gallop rhj'thm was present at the apex. No murmurs
were heard. The edge of the liver was palpable one fingerbreadth below the costal margin.

Roneived for publication Oct. 2.5, 104.5.

.519

520

AMERICAN HEART JOURNAL

Examination of the urine revealed specific gravity, 1.021; pH, 4.0; albumin. Grade 2 (on the
basis of 1 to 4 in vhicii 1 represents the least and 4 the greatest amount of albumin); sugar, nega-
tive- and 7 to 4 ieiicocvtcs per high-power field. Erythrocytes numbered 5,090,000, and leuco-
cvtc-. 17,400 per cubic millimeter of blood. The concentration of hemoglobin was 95 per cent
fSahli). The percentages of the various types of leucocytes were as follows: polymorphonuclears,
7 V staff cells. 7; eosinophils, 2; lymphocytes, 15; and monocytes, 3. The electrocardiogram uas
iitirpretcd as consistent with anterior myocardial infraction (Fig. 1). Roentgenographic ex-
m nation of the thorax revealed elevation of the right side of the diaphragm. There were mot-
1 'cl shadows throughout the entire right pulmonary field with a large circular shadow of increased
d. icitx in the region of the right middle lobe (Fig. 2). The left side of the thorax showed
ixtensivc mottling throughout. Both costophrenic sinuses were clear. The transverse diam-
ittr of the thorax'^ measured 31 cm., and that of the heart was 16 centimeters. The findings
were interpreted as being consistent with pulmonary infarction, but bronchopneumonia could
not be excluded

I-'if;. 1. — Elcctrocardiopram consistent with anterior myocardial infarction.

Routine measures for treatment of congestive heart failure, including administration of
digitalis and complete rest in bed, were begun. Penicillin was likewise admini.stcred in view of
fever, leucocyte count, and roentgenographic e.xamination. Administration of 15,000 units of
penicillin every third hour was continued for seven days. There W'as improvement of dyspnea
.Ttui cough, and in three days the temperature had returned to normal. By December 19 the
gallop rhx'thm had di.sappeared and leucocx’tes numbered 11,700 per cubic millimeter of blood,

ROGERS :

I'

Fig. 2. — Bilateral pulmonary infarcts.

ig. 3. — Bilateral pnoumotliora.x ami )>ilateral pulmonary infarcts.

o22

AxMKRICAN HKART JOURNAL

u'ith 83 per cent polymorphonudears. Beginning December 21, however, there was an elevation
of temperature for two clays to lOl to 102® Fahrenheit. The cough became more severe on
December 23 and wa' accompanied by severe pain in the right side of the thorax without further
elevation of temperature. Roentgenographic examination of the thorax now revealed bilateral
pneumothorax with severe passive congestion in both pulmonary fields and probable regions of
infarction in the inferior lobes (Fig. 3). Since d\-spnca was increased as a result of the bilateral
^jinntaneous pneumothorax, oxygon was administered by means of a tent for three days.

There appeared to be gradual improvement until December 30, when there was observed
^udden severe pam in the upper right quadrant of the abdomen, extending to the right flank and
groin. There was sudden eleeation of temperature to 102° F., and leucocytes numbered 25,050
per cubic millimeter of blood, with 89 per cent polymorphonudears. Analysis of the urine
revealed albumin, Grade 4, with many hyaline and granular casts. A diagnosis of infarction of
the right kidnev, probabh secondary to embolization of the right renal artery, was made. The
condition of the patient became critical with temperature rising to 102® F. and pulse rate to 150
beats per minute. Protodiastolic gallop rh\-thm reappeared. There was a trans’ent drop of
blood pressure to 140/90, but subsequent determinations revealed pressures ranging from 170/130
to 180/140. Nausea and vomiting reappeared and abdominal distention developed.

RIk. 4. — Clear lung fleJcLs.

By Jan. 6, 1945, there was improvement, with disappearance of nausea, vomiting, and ab-
dominal distention. Dyspnea and cough w’ere less troublesome. The temperature returned to'
normal, and the pulse rate ranged from 90 to 100 beats per minute. Roentgenographic e.xamina-
lion of the thorax Jan. 19. 1945, revealed complete resolution of the multiple infarcts and both
lungs were fully expanded (Fig. 4). There were a decrease of the size of the heart and consider-
able decrease of the passive congestion. The condition of the patient at this time had improved
to such an extent that he was dismissed from the hospital.

For the next two months the patient was examined at frequent intervals. Administration
of digitalis and ammonium chloride, restricted intake of fluid, and limited activity were con-

ROGERS: BILATERAL PULMONARY INFARCTION AND PNEUMOTHORAX 523

tinued. The dyspnea and cough did not completely disappear, and toward the end of this period
of observation they increased in severity. These symptoms were now accompanied In' painful
enlargement of the liver, and edema of the ankles appeared for the first time. These manifesta-
tions of right heart failure developed rapidly so that the patient was readmitted to the hospital
March 14, 1945.

, The results of re-examination revealed pulse rate, 100 beats per minute; temperature 98° h'.;
and blood pressure, 170/140 to 176/150. Protodiastolic gallop rhythm -was present. The.
second sound at the pulmonic area was louder than at the aortic area. No murmurs were present.
The liver was palpated for a distance 5 cm. below the right costal margin. Grade 2 edema of
the ankles was present.

Complete rest in bed was instituted and the same medication was continued. In vdew of
the previous pulmonary infarctions, dicumarol therapy was instituted, maintaining the pro-
thrombin time (Quick method) between thirty-five and sixty seconds. As nausea was still severe.
,lanatosid-C \vas substituted for digitalis. Roentgenographic e.\'amination of the thorax revealed
passive congestion in both pulmonary fields. The transverse diameter of the heart had increased
to 20.5 centimeters. On analysis of the urine the albumin was found to be Grade 4 with 16 to 18
hyaline and 7 to 10 granular casts per high-power field. The concentration of nonprotcin nitrogen
was 45.5 itig. per 100 c.c. of serum.

Increasing dyspnea developed and administration of mercurphyllinc injection (mercupurin)
was started.. Satisfactory diuresis occurred; at times as much as 3,500 to 4,000 c.c. of urine in
twenty-four hours was obtained after the intravenous administration of 1 c.c. of mercurphylline.
The manifestations of right heart failure continued and pleural effusions developed bilaterally.
On April 9, 1945, 2,500 c.c. of amber-colored fluid was obtained by right thoracentesis. Sub-
sequently, thoracentesis was done as follows: .April 11, left (1,700 c.c.); April IS, right
(2,000 c.c.) ; April 22, left (1,700 c.c.). There was only slight improvement of symptoms. Death
occurred suddenly on .April 23, 1945, 130 days after the first examination.

Pig_ 5 . — ^l.ung at the edge of the infarct with fibroblasts and newly formed capillaries (X 125).

.At necropsy the following observations were deemed significant: 'I'he heart was moderately
enlarged and weighed 600 grams. The right ventricular wall measured 6 mm. and the left ven-
tricular wall measured 20 mm. in thickness. The left ventricular wall in the anterior apical rt'gion
was thinned to a width of 2 to .1 mm. with formation of an aneury.'im. There was an old, well-

524

AMERICAN HIL\RT JOURNAL

orKanisicd thrombus in the- left ventricle, measuring 6 by 5 by 2 cm. and firmly adherent to the
endocardium beneath the aneurysm. Smaller old mural thrombi were present in the right
ventricle between the trabeculae carneae. The \*alves were normal.

'i’lie coronar>' sclerosis of the left circumflex and the right coronar\- arteries was Grade 2.
The sclero^;-' of the left anterior descending coronary artery was Grade 3 and the artery was
occluded by an old ante-mortem thrombus which originated 1.0 cm. from the bifurcation of the
it ft coronary artery.

There was approximately 1,000 c.c. of amber-colored fluid in each pleural cavitjx Over the
right middle lobe there was a small pleural cj'st, measuring 1.5 by 1.0 by 1.0 cm. and containing
an organired blood clot. The right low-er lobe was atelectatic and contained an organized infarct

FIs;. 0. — Rii;ht KiUnej. a. HyaHnized p:!onie."u!l. iiicreasetl inters-lifial tis'-ue, lympliocyte-s, and niarkctl
medial thickenlny of small arteries {X 90) b. Medium-sized artery ttitli dlssectintt tii>morrliapo dii
the media (x 901.

ROGERS: BILATERAL PULMONARY INFARCTION AND PNEUMOTHORAX 525

measuring 4.0 by 4.0 by 3.0 centimeters. Smaller infarcts were present in the right middle lobe
and the left lower lobe. There were well-organized thrombi in the pulmonary arteries leading
to the right middle and lower lobes and left lower lobe.

In the liver there was the nutmeg appearance of chronic passive congestion.

The right kidney was atrophic and weighed 45 grams. More than three quarters of its
parenchyma was destroyed by old and recent infarcts. The left kidne\' was hypertrophied and
weighed 325 grams. The right renal artery was narrowed by atherosclerotic plaques and meas-
ured 0.5 cm. in circumference, whereas the left renal artery measured 1.5 cm. in circumference.
No thrombi were found in the renal arteries.

Histologic Examination . — In sections of the left ventricle at the site of aneurj'sm, there was
no normal mjmeardium. Most of the myocardium had been replaced by fibrous connective tissue.
A few regions contained old degenerating muscle fibers without nuclei; these fibers were sur-
rounded by fibroblasts. In some regions there were newly formed capillaries. There was a
firmly adherent mural thrombus attached to the endocardium.

There was marked atherosclerosis in the left anterior descending coronarj^ artery. The
lumen was partially occluded by an old organized thrombus undergoing organization and recanali-
zation. In the center there was a recent ante-mortem thrombus which completely occluded the
lumen.

7 _ — Left kidney. Normal glomeruli, tubules, and interstitial tissue with moderate medial thicken-
ing of small artery IX 90).

In all sections of the lung the alveoli contained large numbers of pigment-laden macrophages.
In some regions the alveoli were also filled with erythrocytes and pink-staining edema fluid.
There was medial hypertrophy of the small and medium-sized pulmonary arteries. Small foci
of organization were present, and in a few sections overgrowth of the alveolar epithelium was
seen. There was squamatization of bronchial epithelium in several sections. In the right middle
and lower lobes and left lower lobe old pulmonary infarcts were seen. Organization at the edge.s
of the infarcts was present, as manifested by granulomatous reaction with fibroblasts and newly
formed capillaries (Fig. 5). The pleural cyst over the right middle lobe contained ghosts of ery-
throcytes and fibrin. A granulomatous reaction was present at the edge of the organized blood
clot.

AMERICAN HEART JOURNAL

')2r)

!n the liver the binusoids in the region of the central veins were congested and filled with
erv-throcytes. In the same location foci of necrosis were present.

The sinusoids of the spleen were congested and filled with erythrocytes. There was marked
he.'iHniration of the arterioles.

In the right kidney there were numerous regions of old and recent infarction. Tn the few
- -naining region.s of renal tissue there was marked atrophy with increase of interstitial tissue,
!' a'phocytes, atrophic tubules, and hyalinized glomeruli (Fig. 6, a). Marked medial hyper-
troplv. was proent in arteries and arterioles. In one medium-sized artery there was a dissecting
h-mon-hage into the wall of the media (Fig. 6, 6).

In sections of the left kidney, the glomeruli, tubules, and interstitial tissue appeared normal.
Medial In pertrophy was present but to a lesser degree than that seen in the right kidney (Fig. 7).

The following anatomic diagnoses were made: Hypertrophy of the heart ,(600 grams);
coronary bderosis Grade 2 to 3 with old thrombosis of the left anterior descending coronary
artery; myocardial infarction (old) of the anterior and apical surfaces of the left ventricle with
formation of aneurysm; mural thrombi (old) of right and left ventricles; thrombosis (old) of the
branches of the pulmonary artery to the right middle and, lower lobes and left lower lobe; chronic
[)a'^sive congestion of the liver; arteriosclerotic occlusion of the right renal artery; old and recent
infarcts of the right kidney with atrophy.

COMMENT

In the case presented, hypertensive heart disease was followed by coronary
thrombosis and occlusion of the left anterior descending coronary artery, with
myocardial infarction of the anterior and apical surfaces of the left ventricle.
These changes in turn led to ventricular aneurysm and formation of mural thrombi
in both ventricles. Embolization of the pulmonary arteries and pulmonary in-
farction followed. During the period of acute pulmonary infarction, bilateral
spontaneous pneumothorax developed. The patient recovered from multiple
pulmonary infarction with bilateral spontaneous pneumothorax, but death oc-
curred four months later as a result of right heart failure.

In Marks’* discussion of pulmonary infarction and pneumothorax, he em-
phasized the fact that septic infarcts are more likely to gi^fe rise to pneumothorax
than are uninfected infarcts and stated that, if necrosis occurs within the in-
farcted region and pneumothora.x results, there is likely to be a rapid outpouring
of purulent exudate, thus giving rise to pyopneumothorax. In the first case
reported by Marks, thrombi were observed in the right pulmonary arterj- and
small regions of consolidation were present in each lung. No further description
of the lung was given. In his second case there was gangrene of the middle and
lower lobes of the right lung with empyema. Histologic study of the lungs was
not given in either case.

With pulmonary infarction, secondary infection of the infarcted lung is not
essential for, the production of pneumothorax. In the case reported, the pul-
monary infarcts were probably the result of emboli originating from bland mural
thrombi present in the right ventricle. The popliteal and femoral veins, however,
cannot be entirely eliminated as the source of the emboli. There was no demons-
trable evidence of systemic infection, the infarcts were not secondarih’ infected,
and organization was occurring, as manifested by the granulomatous reaction
at the edges of the infarcts. The histologic appearance of the pulmonarj' in-

ROGERS ; BILATERAL PULMONARY INFARCTION AND PNEUMOTHORAX 527

farcts was consistent with the four-month history, coinciding with the bilateral
spontaneous pneumothorax.

It is not possible to state the exact mechanism of formation of spontaneous
pneumothorax in this case. It is possible that air may have passed directly into
the pleural cavities during the period of pulmonary infarction, as suggested by
Marks. It seems more logical, however, that during paroxysms of coughing,
rupture of the alveoli of the lung occurred, thereby permitting passage of air
into the interstitial connective tissue of the lung. This is in accord with the
view of Hamman,- who expressed the opinion that air gaining access to the inter-
stitial tissue of the lung travels along the pulmonary vessels until it reaches the
mediastinum. The air, having reached the mediastinum, ruptures through the
thin mediastinal wall into the pleural cavity. The bilateral occurrence of spon-
taneous pneumothorax, however, is evidence in favor of mediastinal emphysema
preceding the pneumothorax.'^

It has been reported that spontaneous mediastinal emphysema and pneu-
mothorax may be confused with heart disease.'* In the case reported, hyperten-
sive heart disease and coronary heart disease with myocardial infarction coexi.sted
with spontaneous bilateral pneumothorax. The presence of pneumothorax
superimposed on pulmonary and myocardial infarction not only adds diagnostic
difficulties, but also complicates therapeutic measures.

It is possible that the partial occlusion of the right renal artery with atrophy
and infarction of the kidney played a role in the causation of the hypertension.
The manifestations of vascular disease were more severe in the atrophic than
in the hypertrophic kidney. However, it is realized that it is impossible by gross
examination or histologic study of the kidneys in cases of unilateral renal disease
to state that the atrophic kidney was the cause of hypertension in any specific
case.® It was observed clinically, however, in this case that after one episode of
renal infarction the diastolic blood pressure was higher than it had been before
, the episode. This has been recorded previously.®''^

Dicumarol has received much attention in the prevention of intravascular
thrombosis. It was used in this case as a prophylactic measure five weeks prior
to death, with the hope of preventing any further thrombotic or embolic mani-
festations. During this period of administration of dicumarol, no embolic
phenomena were observed, although congestive heart failure was marked. At
post-mortem examination all thrombi observed in the heart and lungs were old
and probabb' had existed prior to the beginning of dicumarol therapy.

SUMMARY

/

Spontaneous bilateral pneumothorax may occur in association with pul-
mohar^? infarction. Secondary infection of a pulmonary infarct is not essential
for the development of pneumothorax. In the case reported, pulmonary in-
farction was probably secondar}-’ to ancient myocardial infarction. A rise in the
diastolic blood pressure was observed clinically after one episode of renal infarc-

52S

A^rER^CA^• HEART JOURNAL

tion. Dicumarol was used prophylactically with the hope of preventing addi-
tional intravascular thromboses. Additional thrombotic manifestations were
not obseiA'ed after the administration of dicumarol in this case.

REFERENCES

1. Marks, J. H.: Pulmonary Infarction as a Cause of Pneumothorax, New England J. Med.

223: 934, 1940.

2. Haminan, Louis: A Note on the Mechanism of Spontaneous Pneumothorax, Ann. Int.

Med. 13: 923, 1939.

3. Haniman, Louis: Mediastinal Emphysema. The Frank Billings Lecture, J. A. M. A.

128: 1, 1945.

4. J^Iiller, Henry: Spontaneous Mediastinal Emphysema With Pneumothorax Simulating

Organic Heart Disease, Am. J. M. Sc. 209: 211, 1945.

5. Baggenstoss, A. H., and Barker, N. W.: LTnilatcral Renal Atrophy Associated With Hyper-

tension, Arch. Path. 32: 966, 1941.

6. Prinzmetal, Myron, Hiatt, Nathan, and Tragcrman, L. J.: Hypertension in a Patient

With Bilateral Renal Infarction; Clinical Confirmation of Experiments in Animals,
J. A. M. A. 118; 44, 1942.

7. Fishberg, A. M.; Hypertension Due to Renal Embolism, J. A. M. A. 119: 551, 1942.

PURPURIC MANIFESTATIONS OF RHEUMATIC FEVER AND ACUTE

GLOMERULONEPHRITIS

Lieutenant Commander Reverdy H. Jones, Jr., M.C., USNR, and
Lieutenant (J.G.) Williaai W. Moore, M.C., USNR
U. S. Naval Hospital, Portsmouth, Va.

A VARIETY of hemorrhagic conditions, characterized by spontaneous bleed-
^ ing beneath the skin, from the mucous membranes, or into the joints, have
been grouped together under the term “purpura.” The subcutaneous hemor-
rhages appear as small, discrete, purplish spots known as petechiae, or as larger
splotchy, confluent areas referred to as ecchymoses. Purpura, like fever, head-
ache, or pain, is only a sympton or manifestation of an underlying pathologic
condition which in some cases is very evident but in others assumes an idiopathic
nature. The present study is concerned only with simple purpura, without
demonstrable blood changes, as noted in two specific conditions. Purpura of
this type is a manifestation of many diseases and disorders. In some it results
from mechanical causes such as venous stasis or emboli in endocarditis. In others
it is due to acute infectious diseases, most notably cerebrospinal meningitis.
It is also a consequence of nutritional disorders and the administration of certain
drugs, particularly quinine, atropine, and the iodides.

Three cases of symptomatic purpura are presented. In two, the etiology'
was rheumatic fever, and in the third it was acute glomerulonephritis. The first
two cases presented an unusual problem since, due apparently to pure coincidence,
they were admitted to the same sick bay within six hours of each other and with
nearly identical histories. A thorough search revealed no common toxic agent
which might have caused this unusual circumstance. The two men worked
in different places at different types of work, slept in entirely separate barracks,
and ate at different mess halls. One of these cases became even more interesting
when signs of renal disease became so evident that a co-existent diagnosis of
both rheumatic fever and" acute nephritis seemed justified.

CASE HISTORIES

Case 1. — ^\V. K., a 23-year-old Motor Machinist's Mate, Second Class, was admitted to the
sick list Feb. 7, 1945. Three weeks previously he had had acute tonsillitis which had improved
rapidly following the administration of sulfadiazine. Three daj's prior to admission, he began to
have swelling and local heat and pain in the left knee, followed rapidly by migrating polyarthritis.
The next day a red rash appeared over both lower legs, and on the day of admission he had a
severe chill, followed by fever, palpitation, and generalized malaise. The past, occupational
and family histories were negative as concerned rheumatic fevgr, allergy, or exposure to toxic
agents.

Receivetl for publication Dec. 31. 1915.

530

AMERICAN HEAKT JOURNAL

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532

AMERICAN HEART JOURNAL

On admission, the patient was acutely ill and had considerable pain. The temperature was
101°, F., the pulse rate was 90, and the respirations were 20 per minute. The tonsils were large
and chronically infected. The heart was of normal size, with sounds of poor quality, an apical
gallop rhj'thm, and a soft, blowing, apical, systolic murmur which was not transmitted. The
right wrist and both knees were swollen, red, and hot. The spleen was not palpable. Over the
lower legs there was a macular, reddish, discrete, petechial rash, most dense about the ankles
and knees. Initial laboratory studies showed: red blood cells, 3,600,000; a moderate leucocv-
tosis; an clev’ated sedimentation rate of 26 nun, in one hour; and albumin, white blood cells, red
blood cell®, and coarse and finely granular casts in the urine. prothrombin determination, a
platelet count, and a blood culture were normal. An electrocardiogram (Fig. 1) taken on ad-
mi.=sion was normal, but serial electrocardiograms for the next five davs revealed progressive in-
crease of the P-R interval from 0.16 second to a max-imum duration of 0.26 second on the sixth
hospital day. Depression of the S-T segments occurred and was considered to be suggestive of
ventricular myocardial damage. An .\-ray film of the chest and heart was normal.

The diagnosis of acute rheumatic fever with purpuric manifestations, associated with acute
nephritis, was made, and the patient was given sodium salicylate. The prothrombin time de-
terminations, although diminished, remained within normal limits.

Four days after admission the rash had practically disappeared, and after seven days there
remained only a faint pinkish-brown discoloration. The temperature and pulse rate became
normal within seven days, and the joint symptoms rapidly subsided. 'I'he apical systolic murmur
persisted but did not increase in intensity, and the heart sounds became normal. .Seven days
after admission the P-R interval had decreased to 0.24 second; five days later it was normal and
remained so during the remainder of hospitalization. The sedimentation rate remained elevated
and repeated urinalyses continued to show evidence of acute nephritis.

Six weeks after admission the sedimentation rate and all other studies were normal except
urinalysis, which continued to show a trace of albumin. Salic>’late therapy was discontinued.
Two months after admission the patient was allowed out of bed and during the next month his
activities were gradually increased; during this time all studies remained normal

Case 2. — J. L., a 19-year-old Seaman, Fir.st Class, was admitted to the hospital on Feb. 7,
1945. For one week prior to admission the patient h.ad had a slight cold and sore throat, for which
he received no medication. The day prior to admission he noted the onset of a painful swelling
of the left knee and ankle, followed rapidly by the same symptoms in the right knee, then by
the appearance of a rash about the ankles which spread quickly to cover the entire lower legs.
The past, occupational and family histories were negative concerning rheumatic fever, allergy,
or exposure to toxic agents.

On admission the patient was acutely ill and had severe joint pains. The temperature was
99° F., the pulse rate was 94, and respirations were 16 per minute. The heart was normal in
size, its sounds were normal, and a soft s^tolic murmur was audible over the pulmonic area.
The spleen was not palpable. There was local heat, swelling, pain on motion, and tenderness of
the toft knee and both ankles. Over both lower legs there was a deep red. macular, splotchy
rash, in areas so extensive as to apuear confluent (Fig 2).

Initial laboratorx" studies revealed: red blood cells, 3,900,000; a sliyht leucocytosis with a
normal differential count; elevation of the sedimentation rate to 25 mm. in one hour; and a pro-
thrombin determination ^0 per cent of normal. Urinalysis, a blood culture, and a platelet count
were normal.

.■\n electrocardiogram taken on the second hospital dav rex'ealed a pronounced sinus arrln-
thmia with a -bradycardia, a varying P-R interx-al, and ventricular escape. Two flax's later the
electrocardiogram showetl no significant change except a decreased nodal irritabilitx'. On the
fourth hospital day the electrocardiogram returned to normal and remained so throughout hos-
pitalization (Fig. 3). .An x-ray film of the lungs and heart was normal.

On the second hospital day the temperature rose to 102° F. and there was an exacerbation
of the migratory polyarthritis inx'olx'ing the right elbow and wrist.

.‘\ tentative diagnosis of acute rheumatic fex'er xvilh purpuric manifestations was made, and
the patient xvas placed on sodium salicylate therapx*. nnring thi.s time the re-ults of the pro-

JONES, JR., AND MOORE; RHEUMATIC FEVER AND GLOMERULONEPHRITIS 533

thrombin determinations declined but remained v.'ithin normal limits. Four days after admission
the temperature and pulse were normal, the joint sj^mptoms had disappeared, and the rash had
faded considerably. The sedimentation rate remained elevated but all other laboratory proce-
dures were normal. The sedimentation rate became normal five weeks after admission. The
patient was then allowed out of bed and salicylate therapy was discontinued. During the next
month, all studies remained normal, there were no further symptoms or complaints, and the
patient’s activities were gradually increased.

Fig. 2. — Case 2. The rash at the height of the illness was macular in type and fleep red in color. It
was pro-sent over both lower legs and so extensive that it appearcxl to be confluent.

Cask 3. — F. B., an 18-year-old .Seaman, Second Cla.ss, was admitted to the hospital on Feb.
25, 1945. Two weeks previously he had had a mild upper respiratory infection for which he was
given fifteen sulfadiazine tablets. Ttvo days before admission a rash appeared over both lower
legs and spread rapidly during the next thirty-six hours to involve the entire lower extremities.
Except for mild soreness associated with the rash, the patient had no complaints. The past,
occupational, and family histories were negative for rheumatic fever, allergj-, or exposure to toxic
agents.

On admission the patient was found to be well developed and well nourished and in no dis-
tress. The temperature was 99.8° F., the pulse rate was 100, and the respirations were 20 per
minute. The throat appeared normal. No abnormality of the heart was apparent. The
spleen was not palpable. Over the lower extremities there was a diffuse, dark, wine-red, macular,
mottled rash, in places so extensive as to be confluent (Fig. 4).

Initial laboratory studies revealed: moderate anemia; red blocd cells, 3,300.000; slight
leucocytosis with a normal differential count; an elevated sedimentation rate of 27 mm. in one
hour; a prothrombin determination of 72 per cent of the normal; and a normal platelet aount.
-A blood culture taken on admission was negative. Electrocardiograms on three occa.sions witc
normal. Urinalysis revealed only a trace of albumin.

The exanthem rapidly subsided after two days, but the patient continued to have a low-
grade fever. Urinalysis showed evidence of nephritis with albumin, red and white blood cells,
and casts. The persistent urinary finding.s were consistent with a clinical diagnosis of acute
glomerulonephritis.

534

AMERICAN HEART JOURNAL

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»~‘'cnt!ally the same ftntiinps. Tracincs made on awl after T'eh. 10, 191,5. nere normal. Illustration
continiit<l on opposite page.

JO>rES, JR., AND MOORE:

2/10/45 Z/r> 4o

Ficr. 3 (Cont’d ). — For legend, see opposite page.

FiK. 4. — Caso 3. On admission to thn hospital, there was a dark wine-red, macular rash over botli
lower extremities. The ra.sh was extensive and in places confluent.

53G

AMERICAN heart JOURNAL

On the eighth hospital day the patient began to have transitory pains in both knees and the
right elbow of twenty-four hour’s duration without any positive physical findings. Otherwise
there were no rheumatic manifestations.

Two months after admission the patient had no complaints and physical examination was
completely negative, but the sedimentation rate continued elevated and the urinary findings con-
tinued to show evidence of nephritis.

DISCUSSION

The clinical association of rheumatic fever with cutaneous nodules and
erythematous and hemorrhagic eruptions has been recognized for many years.
Wells' and then Bright' in 1831 recorded instances of an exanthem in rheu-
matic fever and credit has been given to Rayer- for being the first to describe
the association of er}'’thema multiforme with acute rheumatic fe\er in 1835.
Among the more prominent cutaneous manifestations of acute rheumatic fever
are tJie following:

a. The rheumatic erythemas including erjThema multiforme, eryThema
annulare, and erythema marginatum. Of these, eiy'thema multiforme
is by far the most prevalent.

b. Hemorrhagic eruptions including purpura. This group is distinct from
purpura rheumatica or Schoenlien’s purpura in which the association
with rheumatic fever is uncertain.

c. Subcutaneous nodules.

d. Erythema nodosum.

Although the estimated incidence of cutaneous manifestations in rheumatic
fever has varied from 4 per cent to over 75 per cent, the im.pression prevails
that this condition is infrequent. In a review of rheumatic fever for 1941,
Hench® stated that 5 per cent of the cases demonstrated skin lesions. Keil,'*
in a summary of 523 cases of acute rheumatic fever, found that 10 per cent had
erythematous lesions. Swift^ mentions the occurrence of various skin manifes-
tations. White® stales that this condition may occur in from 2 per cent to 75
per cent of patients with rheumatic fever, the percentage vaiydng in different
groups and in different parts of the world. According to this author eiyThema
mulliforme is the commonest of the skin lesions and occurs at some period in
15 per cent of all cases of acute rheumatic fever. -In this hospital over the past
six months there have been sixty-three admissions for acute rheumatic fever,
of which three, or 4.7 per cent, demonstrated cutaneous lesions.

Thus, the general incidence of rheumatic cutaneous lesions is low and the
specific appearance of purpura as a skin manifestation is even more rare. Han-
sen' refers to purpura as being a cause of mistaken diagnosis in only one case
in a review of 167 patients with rheumatic fever; and in a further review of 271
cases he mentions purpura as a rare possible source of confusion in the initial
diagnosis of rheumatic fever. Both White and Swift refer to purpuric manifes-
tations as occasionally seen. Lichtwilz® mentions purpura as occurring in rheu-

JONES, JR., AND MOORE: RHEUMATIC I'EVER AND GLOMERULONEPHRITIS 537 ,

made fever and considers it a systemic disorder centering in the capillaries
which is less severe and distinct from the so-called Henoch’s purpura sometimes
seen in other infectious conditions.

Purpura, associated with acute glomerular nephritis, appears even more
infrequently. Minod^ mentions purpura as being very rarely associated with
chronic nephritis. Fishberg,^^ in discussing acute glomerulonephritis, states
that purpuric spots occasionally appear in small numbers.

The relationship between acute rheumatic fever and acute nephritis has
, received extensive study in the past few years. It is felt that generalized involve-
ment of the vascular system is a common accompaniment, if not a constant
manifestation, of the rheumatic process. The most common pathologic finding
in rheumatic fever has been described as a nonsuppurating, perivascular infil-
tration, affecting chiefly the smaller vessels, associated with edema and round
cell infiltration, and leading to the formation of new connective tissue. Although
these changes are most frequently found in the myocardium and endocardium,
they have been described as affecting the coronary arteries as well as the renal
vessels.

It is well recognized that acute glomerulonephritis in association with acute
rheumatic fever is very rare. Hutton and Brown^’ state that in large groups of
patients who have acute rheumatic fever, nephritic complications vary from
0.67 to 7 per cent. These authors described four cases of rheumatic fever with
clinical evidence of nephritis, in which a typical rheumatic endarteritis, asso-
ciated with characteristic Aschoff bodies, was demonstrated at autopsy in both
the myocardium and kidneys. Blaisdell,*^ in a review of sixteen autopsied pa-
tients with rheumatic fever, found typical perivascular infiltration present in
the kidneys in fourteen cases. The primary lesions were in the interstitial tissues
and the degenerative hyaline changes observed in the glomeruli were felt to be
nutritional disturbances secondary to the interstitial vascular changes. Blais-
delfli felt that "while the changes noted are of most frequent occurrence and
give rise to a definite interstitial nephritis, the renal damage is only occasionally
of sufficient degree to lead to a diagnosis of kidney disease during life.’’

From the literature it can be accepted that acute rheumatic fever is a
disease resulting in widespread pathologic changes. It well may be that the
purpuric lesions are themselves a part of this generalized process. Deterioration
of the capillary wall, with red blood cells escaping through these capillary defects,
is considered to be the underlying cause in this type of purpura. The associated
renal lesions and, at rare intervals, the clinical evidence of nephritis, lends further
evidence of the generalized nature of the rheumatic infection. It is noteworthy
that while acute glomerulonephritis associated with rheumatic fever, even
subclinically, is rare, renal lesions of an interstitial nature are observed relatively
frequently, although, here again, clinical manifestations are unusual. The high
incidence of cardiac involvement and the occasional presence of skin lesions
may perhaps be evidence of a similar generalized pathologic process in acute
glomerulonephritis. It is of interest and importance that skin le.sions or pur-

538

AMERICAN' HEART JOURNAL

pura can be an initial symptom of these Iavo maladies, and this fact should empha-
size the necessity of searching for the underlying pathogenesis in patients ad-
mitted to the hospital with this symtomatic diagnosis.

SUMMARY

1. Three cases of symptomatic purpura have been presented. In two of
these the underlying factor was considered to be acute rheumatic fever, in one
of Avhich there was evidence of simultaneous nephritis. The primary cause in
the third case was acute glomerulonephritis.

2. The various cutaneous manifestations of acute rheumatic fever and
acute glomerulonephritis have been outlined.

3. The nephritic manifestations of rheumatic fever have been discussed
together with the relationship between these two conditions.

REFERENCES

!. Wells, W. C.; Bright, R.: Quoted by Keil, H.: Ann. Int. Med. 11: 2223-2273, 1938.

2. Rayer: Quoted by Keil, H.; Ann. Int. Med. 11: 2223-2273, 1938.

3. Hench, P. S., Bauer, W., Christ, D., Hall, F., Holbrook, W. P., Key, J. A., and Slocum, H.:
The Present Status of Rheumatism and Arthritis, Review of American and English Litera-
ture for 1936, Ann. Int. Med. 11: 1089-1249, 1938.

4. Keil, H.: The Rheumatic Ervthema; A Critical Sur\'ey, Ann. Int. Med. 11: 2223-2273,
1938.

.i. Swift, H. F,: Section on Rheumatic Fever, in Cecil, R. L.: Te.Ktbook of Medicine, ed. 6,
Philadelphia, 1944, W. B. Saunders Company, pp. 99 and 443.

6. White, P. D.: Heart Disease, ed. 3, New York, 1944, The Macmillan Co., p. 241.

7. Hansen, A. E. : Staff Meeting Bulletin, Hospital-University of Minnesota, vol. xii. No. 5,
November 1, 1940.

8. Hansen, A. E.; Conditions Causing Confusion in the Diagnosis of Rheumatic Fever in
Children, J. A. M. A. 121: 51, 1943.

9. Lichtwitz, Leopold: Pathology and Therapy of Rheumatic Fever, New York, 1944, Gnme
and Stratton.

10. Minot, G. R.: Section on Purpura, in Cecil R. L.: Te-vtbook of Medicine, Philadelphia,
1944, W. B. Saunders Company, pp. 99 and 978.

11. Fishberg, .A. M.: Hypertension in Nephritis, ed. 4, Philadelphia, 1940, Lea and Febiger.

12. Hutton, R. L., and Brown, C. R.: The Renal Lesion in Rheumatic Fever, Ann. Int. Med.
20; 85-98, 1944.

Blaisdell, J. L.: The Renal Lesions of Rheumatic Fever, Am. J. Path. 10: 287-297, 1934.

13.

Abstracts and Reviews

Heirmann, G. R.: Blood Plasma Proteins in Patients With Heart Failure. Ann. Int.

' Med. 24:893 (May), 1946.

This report is an analysis of blood protein estimations before and after dissipation of the
edema in. 100 patients with congestive heart failure. The results showed slight but definiteU'
subnormal albumin values with slight compensatory increases in globulin values during the
edematous stage. After the dissipation of the edema, the blood proteins did not immediately
rise to normal levels, but there were gradual accretions. It is suggested that this lag is due to the
fact that the liver cannot assist with protein anabolism until circulatorj' equilibrium is re-estab-
lished. The lowest blood protein levels were noted in patients who had suffered congestive failure
for many months. VVkndkos.

.Andersoa, D. P., Allen, W. J., Barcroft, H., Edholin, O. G., and Manning, G. W.: Cir-
culatory Changc-s During Fainting and Coma Caused by O.vygen Lack. J. Physiol.
104:426 (April), 1946.

Healthy male subjects, aged twenty to thirty years, reclining with the back supported at an
angle of about 45 degrees, breathed o.\'ygen -nitrogen mi.\tures containing appro.vimately 10, 8, 7,
and 6 per cent oxygen. The pulse rate, arterial blood pressure, and forearm blood flow fplethysmo-
graphic) were recorded. Among thirteen subjects, there were three fainters and ten nonfainters.
A t3fpical test in a fainter consisted of an initial rise in pulse rate, sj'stolic arterial pressure, and a
slight increase in forearm blood flow followed by vasov'agal syncope, during which both the systolic
and diastolic pressures and the pulse rate fell below control levels. Nonfainters, however, lost
consciousness without showing any signs of the vasovagal reaction and maintained their tachy-
cardia and elevated sj’stolic pressure for the duration of the hj’poxic period. In both the fainters
and nonfainters forearm blood flow rose to significantly high levels.

In the same group of subjects hypoxia was superimposed upon a simulated hemorrhagic
state induced by trapping blood in the lower extremities by means of venous tourniquets. In
this “posthemorrhagic” hj'poxia a much higher percentage of vasovagal syncope was encountered:
ten of the thirteen subjects fainted. The circulatory reactions in this group of experiments
were, on the whole, the same as those observed in vasovagal syncope caused by simple hypoxia.

The increase in forearm blood flow in vasovagal syncope and in coma due to hypoxia is con-
sidered to be due to vasodilation in skeletal muscle.

It is suggested that wounded men who have lost significant quantities of blood may need
oxj’gen in an atmosphere of low’ oxygen tension . FriedI-AXO.

Levy, L., ami McKrilI,N.: Results in iheTrealment of Subacute Bacterial Endocarditis.

'Arch. Int. Med. 77:367 (.April), 1946.

These authors present a rather complete review of the literature relating to the thenipy of
subacute bacterial endocarditis in the past, and record the results of their own treatment in
eleven patients. Their plan of treatment consisted of the administration of 200,000 units of
penicillin intramuscularly in divnded doses every two hours. Sulfadiazine, in a dosage of 1 Gm.
every four hours day and night, was also administered with the penicillin. Nine patients re-
ceived heparin dissolved in 1,000 c.c. of a 5 per cent solution of de.xtrosc in distilled water

.->10

AMERICAN' HEART JOURNAL

a? a continuous intravenous drip. The amount of heparin given vas that required to main-
tain a clotting time of between thirty to sixty mimitc.s; in twenty-four hours, tin's varied between
90 to .lOO mg. (9 to 30 c.c.L During heparinization, frequent reactions were observed. These
consisted of fever, sometimes with a temperature up to 108“ F., chills, mild e.xcitement, and some
flisorientalion. .Some of these reactions were believed to be due to the release of protein from the
decomposition of bacteria, some to heparin sensitivity, some to embolic phenomena, and some were
not explainable. Of the eleven patients, seven were considered to be probably cured; one died
from a heparin reaction, and three failed to recover. As a result of autopsy in four cases, they
conclude that heparinization favors fragmentation of the vegetation leading to embolism, and that
large cerebral hemorrhages are due to bleeding into infarcted areas as a result of the diminished
coagulability of the blood. As a result, they advi.se heparinization only in a few selected cases.

j\ftcr the patient recovers from an cpi.sode of subacute bacterial endocarditis, they suggest
frequent follow-up examinations and elimination of foci of infection. Biit.i f.t.

iMcIntosTi, IJcrkclcy C,. and .lackson. Robert L. ; Angles of Clearance: A Method for
IVIeasuring the Cardiac Size of Children With Khctimalic Heart Disease (A Compari-
son With the Cardiothoracic Index)* Am. J. Dis. Child. 71:357 (April), 1946.

The use of the angle of clearance as a fluoroscopic method for measuring cardiac size was
devised by Wil.son in 1934. After comparing it with other methods of measuring the size of the
heart of patients with rheumatic heart disease, she concluded that the angle of clearance differen-
tiated the normal from the abnormal with greater frequency.

Jackson studied this angle and its reliability as a measurement of cardiac size in 194,1 and
established normal values for children using a modified technique. The most significant changes
were the measurement of two angles instead of one and the designation of these as the first and
second angles of clearance. The first angle is that at which the left dorsal border of the heart
separates from the transverse process of the vertebrae and the second is that at which the left
dorsal border of the heart clears the anterior surface of the vertebral bodies. Wilson had originally
e.stablished the upper limit of normal for this second angle as 55 degrees. Jackson found the mean
value for the first angle to be 51 .8 degrees and for the second angle, 63.2 degrees. The standard
deviations were 5.8 and 7.4, respectively. Sixt}--one patients with inactive rheumatic heart disease
and sixteen with active disease are the basis for this report. Comparison was made with the heart
sizes obtained by using the cardiac thoracic diameter and physical examination.

Of the entire group of seventy-seven subjects, 68 per cent showed a second angle of clearance
above the selected high normal limit of 70 degrees. Forty-one per cent were above the high normal
of 57 degrees as measured by the first angle. Thus the second angle of clearance indicated enlarge-
ment in a higher percentage of cases than did the first angle The cardio-thoracic angle was above
norma! in only 35 per cent of children. However, if the group of children with a considerable
degree of enlargement are eliminated, this difference became even greater and in this group the
percentages for the two angles arc 41 per cent and 12 per cent, respectively. The cardio-thoracic
ratio detected enlargement in none of these cases. ,

The angles of clearance arc capable of showing lesser degrees of cardiac enlargement than is
the cardio-thoracic diameter and are a valuable adjunct in detecting changes in heart size aiused
b\ rheumatic fever. However, the trends of both are parallel in any given subject and both are
of value in following an individual subject. H.\un.

(.ri.s’tic, II. Penicillin in Stihnciilc Baclcrlnl Endocarditis: Report to llic IMcdical
Research Council of 147 Patients Treated in 14 Centers Appointcil by the Penicillin
Clinical Trials Coinmittee. Brit. M. J. 1:381 (March 16), 1946.

Thi.s report cover.s an eighteen-month period. Fifty-five per cent of the patients were
“cured, ’ at least for the duration of the four- to eight-month observation period. There were
fifty death'- (34 per cent); in the remaining 1 1 per cent, the final outcome could not be stated with
certainly. .\ !-lreptoco<Tu> was the infecting agent in all cases but one; the majority of cases
was found to be infected by Streptococcus viridans. Penicillin was administered every three
hours intrarmi-cularly nr as a continous intramuscular drip with about equal success.

SELECTED ABSTRACTS

541

By increasing the period of treatment, using the same total dose (5,000,000 Oxford units),
the results improved steadily. With five-day courses, no cures and 70 per cent relapses occurred.
Twentj'-day courses cured 50 per cent, with a relapse rate of 21 per cent: figures almost twice as
high as the percentages obtained with ten-day courses. The best results were obtained with a
total dosage of 14,000,000 units in twenty-eight day courses: 61 per cent appeared “cured" during
the follow-up period, and no relapses were obserx'ed. The duration of treatment was thus the
most important factor, but the size of the dose was also important: large doses were more effec-
tive. The death rate was relatively constant for each of the groups, ranging between 17 and 40
per cent, with an average of .30 per cent. Relapses usiialh- occurred within thirty days and almost
always within fiftj'- days of cessation of therapy. Short, inadequate courses did not prejudice
later results with full doses. Although the many relapses were usually early (within a week)
the re-treated patients met the averages obtained for the series. Those who did poorly with
adequate dosage, though their relapses were longer in appearing, also did poorly when their courses
were repeated. A relapse after a twenty-eight daj’ course was serious and justified a six- to eight-
week re-treatment period? for the recovery rate was statistically only one-half that of the average
obtained for the series. The reason for this was apparently not in the increased resistance of the
organism, since this could be demonstrated in onlj^ a small minority and was never great. It
was concluded that these patients therefore represented a selected group which had a poor response
to antibiotic therapy.-

In vitro resistance, expressed as multiples of the resistance of the standard Oxford Staphylo-
coccus, was of clinical value only if very great.

Clinical results Avere as good with “resistant” organi.sms (compared with the Oxford Staphylo-
coccus) as with “sensitive” strains. Of three patients who had strains more than thirty-two times
as resistant as the Oxford Staphylococcus, two died of ovenvhelming infection. The third patient
recovered on a twenty-one day course of 5,200,000 units every twenty-four hours.

Observations on the importance of removing foci of infection and the role of congestive heart
failure in the causation of the majorit}’^ of the deaths were in agreement with reports in current
American literature. It was concluded that although excellent results would occur occasionally
with anj' system of dosage lasting for more than ten days, relapses would be unnecessarily frequent
unless 5,000,000 units were given for twenty-eight days as routine therapy in all proved cases.

.S.-VYEK.

Jensen, C. R.: Non-Suppurative Post-Streptococcie (Rhciimalie) Pneumonitis. .Arch.

Int. Med. 77:237 (March), 1946.

The author points out that clinical recognition of the pulmonary lesions in rheumatic fever is
increasing, but confusion still occurs in the differential diagnosis of this type of pneumonitis.
Jensen presents the clinical -pathological findings in a 19-year-old male who died thirty days after
the onset of an initial attack of rheumatic fever, featured at first by typical scarlet fever and soon
followed bi' arthritis, nephritis, and pneumonitis. .An apparently satisfactory convalescence from
scarlet fever was interrupted on the fifteenth day by polyarthritis, dyspnea, hemorrhagic nephritis,
and acute hypertension. Under salicylate therapy, the arthritis subsided and the azotemia was
reduced. Dyspnea, however, was increased and eventually was accompanied by ejanosis. .An
electrocardiogram was normal. RSles were audible throughout both lungs. The patient died in
great respiratory distress exactlj- thirty days after the appearance of a streptococcic pharyngitis
and fifteen days after the onset of rheumatic pain.

Post-mortem examination showed large lungs, only slightly crepitant, quite solid and plum
purple in many areas but not hard and friable. Micro-scopy revealed monocytic infiltrations in
the alveolar walls, consisting of swollen endothelial cells, large mononuclear type lymphocyte.s, and
plasma cells. Some small but dense collections of these cells were noted, but a true .\schoff body
was not found. Special stains were negative for organisms. The alveoli contained edema fluid,
many ervthrocytes, desquamated alveolar cells, monocyte.-^ and a generally sparse infiltration of
poh'morphonuclears.

The kidneys showed focal interstitial hemorrhage and perivascular lymphocytic and plasma
cell collections. Many tubules contained blood, but the glomeruli were rather bloodless.

5-12

AMERICAN HEART JOURNAL

The hearL, which was normal grossly, showed small pericardial and also endocardial collections
of lymphocytes and plasma cells histologically.

The author emphasizes the unusual opportunity that was presented in this case to study the
pulmonary lesions of rheumatic fever uncomplicated by secondary infection or by changes second-
ar}' to heart disease. He describes rheumatic pneumonitis as a non-suppurative tissue reaction
similar to that seen in other organs following hemolytic streptococcic infection of the upper respira-
tory tract; in somtf ‘instances it was so pronounced as to dominate the clinical picture. Jensen
points out the possibility of error in diagnosing such a pulmonary invoK'ement as a virus pneu-
monitis. He recommends more e.\tensive use of the cold pressor and of the antistreptolysin tests
in differential diagnosis. Goui-hy.

Hicks, A. i\I., Painton, J. 1'., and Hantman, S.: A Clinical Analysis of Primary Atypical

I’ncnmonia, With a Discussion of tlic Elect rocardiograpliic Findings. .Ann. Int.

Med. 21:775 (May). 1946.

This report is based upon an analysis of 321 cases of atypical pneumonia studied in one of the
military hospitals in this country during the recent war. Correlations were established between
the incidence of the disease and the age, race, weight, length of service, and the season of the year.
The clinical features and laboratory findings were reviewed, and the conclusions reached were
found to be similar to tho.se expressed in previous reports concerning atypical pneumonia. The
same statement was true of the roentgen patterns and the authors’ comments concerning treat-
ment of this disease. Electrocardiographic c.xaniinations were employed e.xtensively in sixty-
three cases, and twelve of this group showed “electrocardiographic evidence suggestive of myo-
cardial and pericardial involvement.’’ Only two of these patients presented clinical evidence
suggestive of cardiac abnormality. The changes consisted of RS-T segment elevations, T-wavc
inversion, a disturbance of A-\’ conduction, or combinations of these. In seven of the cases there
was electrocardiographic reversal to normal, whereas the other five showed irreversible changes
which persisted throughout a three-month period of observ.ation. None of the rases came to
autopsy. WivNDKOS.

IJlnnkcnborn, M. Villcr. C. F,, Scheinkcr, 1. M., and .Austin, R. S.: Beriberi Heart

Disease. J. A. M. A. 1,31:717 (June 29), 1946.

These authors report their study of a series of twelve cases which were diagnosed as beriberi
heart disease from 1940 to 1945. Five patients died in the hospital; autopsies were performed
on three patients. The authors believe that the oriental concept of beriberi heart disease a«
characterized by Wenckebach criteria probably has hindered the diagnosis in many instances.
This is particularly true in the large group of cases of beriberi heart disease which do not manifest
the rapid circulation and which closely resemble other types of degenerative heart disease. The
requirements for diagnosis in their series were (I) insufficient evidence of other etiology; (2) three
or more months on a thiamine-deficient diet; (3) signs of neuritis or pellagra; (4) enlarged heart
with sinus rhythm; (5) dependent edema; (6) elevated venous pressure; (7) minor electrocardio-
graphic changes; (8) recovery with decrease in heart size; or (9) autopsy findings consistent with
beriberi heart disease. The chief factor in diagnosis includes the realization that the etiologir
nature of the heart disease is obscure. The dilTerential diagnosis includes coronary arterios-
clerosis. Fiedler’s myocarditis, and idiopathic hypertrophy.

Alcoholism accounted for the poor dietarie.s of eleven patients. The majority of diets
were deficient not only in thiamine, but also in the other water-soluble vitamins, particularly
niacin, riboflavin, and ascorbic acid. .Although the time interval required to produce the degree
of hypovitaminosis sufficient to produce cardiac abnormalities varies considerably in different in-
dividuals, ninety days is the arbitrary point selected. In all twelve cases there was other clinical
evidence of nutritive failure. There was always .some indication of peripheral neuritis or pellagra.
In six cases evidence of both di.sorders was found. Eight of the twelve patients had anemia, which
in three in'-tances was normocytic anrl in five macrocytic in type. Hypoprotcinemia Was con-

SELECTED ABSTRACTS

543

sistently observed in these patients. Ten of the patients during life showed clinical and roent-
genologic evidence of cardiac enlargement. Dependent edema was present in eleven of the twelve
patients, and elevated venous pressure was observed in nine. Serial electrocardiograms were
made in ten of the twelve cases and all showed abnormalities. The most common abnormalities
observed were low voltage and minor alterations in the 'I' waves.

'.When beriberi heart disease was suspected, the patient was put on a strict regimen which
included rest in bed and a diet very low in thiamine. The control period was continued as long
as the patient’s condition permitted. Large doses of thiamine were then given intravenously.
Most cases which showed improvement did so gradually: only one showed dramatic improvement
in a period of twenty-four hours. Three of five patients who received digitalis apparentl}.' bene-
fited from this drug. There is some uncertainty as to the origin of the dictum that digitalis is
of no aid in this condition and that if the heart responds well to this drug the diagnosis of beriberi
is eliminated.

While alterations in the myocardium in beriberi heart disease have been described an<l
studied repeatedlyTor many decades, no pathognomic picture has been revealed. Three of their
cases which came to necropsy showed degenerative changes of the heart muscle and interstitial ,
edema. These observations were considered consistent with but not diagnostic of beriberi heart
disease. In two instances in which the nervous system was examined, definite lesions in the cen-
tral, peripheral, and autonomic nervous systems were revealed. Bneun'.

Nathansoii, M. H. s Hyperactive Cardioinhibitory Carotid Sinus lleflcx. Arch. Tnt.

Med. 77:491 (May), 1946.

This report was based on a study of 115 patients showing hyperactive carotid sinus refle.xcs.
The carotid sinus was considered hyperative when it fulfilled the following criteria: (1) a cardiac
standstill of at least five seconds; (2) cardiac inhibition induced by simple pressure on the carotid
sinus without massage of sinus; (.3) standstill of equal intensity elicited on several tests. The
youngest patient was 30 and the oldest in the group was 81 years of age; the average age was 58.9
years. Of the 115 patients, seventy-seven (67 per cent) presented no symptoms suggestive of
carotid sinus syndrome. In ten cases, manifestations of the carotid sinus syndrome were the
chief complaints. .Attacks of syncope were experienced by only six patients. Symptoms resem-
bling those of carotid sinus syndrome were presented by fifteen patients, but some mechanism ,
other than the hyperactive carotid sinus reflex could be demonstrated as a basis for the attacks.
In five of these patients, there was a true vertigo with nausea and tinnitus, indicative of Meniere's
:S 3 'ndrome. The sensations following pressure on the carotid sinus had no similarity to the sensa- ,
tions at the time of the spontaneous attacks. In four patients, the symptoms of faintness and dizzi-
ness were associated with attacks of paro.xysmal tachycardia.

A definite distinction is made between the hyperactive carotid sinus reflex which designated a
hyperactive response to stimulation of the carotid sinus and the carotid sinus syndrome which
designated a clinical condition. The author explains the presence of symptoms in some and the
absence of symptoms in others with similar degrees of sensitivity to a difTerence in individual re-
sponse to cerebral ischemia.

This author also made an attempt to determine the site of the hyperactive cardioinhibitory
refle.x. Pressure over the carotid sinus was shown b\‘ Hering to elicit two independent effects:
f1)' a cardioinhibitory effect and (2) a vasodepressor effect. The former may be abolished by.
atropine, permitting observations of the vasodepressor effect. Blood pressure readings were taken
during stimulation of the carotid sinus, before and after administration of atropine. • It wasob- ,
served that there was definite lowering of the blood pre.ssurc following carotid sinus stimulation
in the atropinized patient. He therefore concludes that either the vagus center in the medulla,
or some portion of the efferent path in the vagus nerve must be considered responsible for the
hyperactive response. This observation is of practical importance becau.se denervation of the
carotid sinus would not insure a consistent and permanent cure if the hypersensitivity was pre-
dominantly in the vagus nerve. BF.tXFtT.

American Heart Association, Inc.

1790 Broadway at 58th Street, New York, N. Y.

IJk. Rov \V. Scott
President

Dr. Howard F. West

Vice-President

Or. George R. Herrmann
Treasurer

Dr. Howard B. Sprague
Secretary

BOARD OF DIRECTORS

Dr. Edgar V. Allen Rochester, Minn.

Dr. Gr.aham Asuer Kansas City. Mo.

*Dr. Arlie R. Barnes Rochester, Minn.

Dr. Alfred Blalock Baltimore

•Dr. William H. Bunn Youngstown. Ohio

Dr. CI.ARKNCE DE LA CiiAPELLE. .New York City

•Dr. Tinsley R. Harrison Dalla.-!

Dr. George R. Herraunn Galveston

Dr. T. Duckett Jones Boston

Dr. Louis N. Katz Chicago

Dr. Samuel A. Levine Boston

Dr. Gilbert Marouardt Chicago

•Dr. H. M. Marvin. . . . .’ New Haven

•Or. Edwin P. Maynard. Jr Brooklyn

•Dr. Thomas M. McMillan Philadelphia

Dr. Jonathan Meakiks Montreal. Can.

Dr. E. Sterling Nicnol Miami

•Executive Committee.

Dr. Harold E. B. Pardee . . .New York City

Dr. William B. Porter Richmond, Va.

•Dr. David D. Rutstein New York City

♦Dr. John J. Sampson San Francisco

Dr. Rov W. Scott Cleveland

♦Dr. Howard B. Sprague Boston

Dr. George F. Strong. Vancouver, B. C.. Can.

Dr. William D. Stroud Philadelphia

Dr. Homer F. Swift New York City

Dr. William P. Thompson . ... Los .Angeles

Dr. Harry E. Ungerleider. . New York City
♦Dr. Howard F. West .... ... Los Angeles

Dr. Paul D. White Boston

Dr. Frank N. Wilson Ann .Arbor

♦Dr. Irving S. Wright New York City

Dr. Wallace M. Yater . . Washington. D. C.

Dr. H. M. Marvin, Acting Executive Secretary
Anna S. Wright. Office Secretary
Telephone. Circle 5-8000

T he American Heart .Association is the only national organization devoted to
educational work relating to diseases of the heart. Its activities are under the
control and guidance of a Board of Directors composed of thirty-three eminent phy-
sicians who represent every portion of the country.

A central office is maintained for the coordination and distribution of important
information. From it there issues a steady stream of books, pamphlets, charts, films,
lantern slides, and similar educational material concerned with the recognition, pre-
vention, or treatment of diseases of the heart, which are now the leading cause of death
in the United States. The American Heart Journal is under the editorial super-
vision of the Association.

The Section for the Study of the Peripheral Circulation was organized in 1935
for the purpose of stimulating interest in investigation of all types of diseases of the
blood and lymph vessels and of problems concerning the circulation of blood and lymph.
Any physician or investigator may become a member of the section after election to
the .American Heart Association and payment of dues to that organization.

The income from membership and donations provides the sole financial support
of the Association. Lack of adequate funds seriously hampers more intensive edu-
cational activity and the support of important investigative work.

Annual membership is $5.00. Journal membership at $11.00 includes a year's
subscription to the American Heart Journal (January- December) and annual mem-
bership in the .Association. The Journal alone is $10.00 per j’ear.

The Association earnestly solicits your support and suggestions for its work.
Membership application blanks will be sent on request. Donations will be gratefully
received and promptly acknowledged.

r.4A

American Heart Journal

VoL. 32 November, 1946 No. 5

Original Communications

RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE IN
THE NORTH AFRICAN AND MEDITERRANEAN THEATER
OF OPERATIONS, UNITED STATES ARMY

Lieutenant Colonel Edward F. Bland
Medical Corps, Army of the United States

introductory remarks

T he present study was undertaken on behalf of the Surgeon, Mediterranean
Theater of Operations, United States Army, to determine the incidence of
rheumatic fever and of rheumatic heart disease in Army personnel in this Theater,
to observe the effect of wartime conditions upon their clinical course, to appraise
the policies adopted for their management, and, finally, to scrutinize the measures
now in force- for the exclusion of susceptible individuals from overseas assign-
ment. The material upon which this report is based consists essentially of both
combat and service troops of the United States Army involved in this Theater
from the original landings in North Africa in November, 1942, through the
Tunisian, Sicilian, and Italian campaigns to the end of hostilities in Ma}'-, 1945.

Two factors largely determined the method of approach adopted in assem-
bling the data. First, in view of the now well-recognized chronic nature of
rheumatic fever and the disabling effects of valvular heart disease developing
therefrom, hospitalization and disposition of these patients overseas were essen-
tially functions of the general hospitals. Second, approximately 95 per cent
of the patients involved either were boarded for the Zone of the Interior (the
United States) or for limited service, and copies of the board proceedings con-
taining pertinent clinical data were retained by the hospitals and were available
for review. Therefore, a study of the clinical records and of the board proceed-
ings of the general hospitals is the basis for the greater part of the factual data
recorded herein.

Received for publication Jklarcb 23, 104G,

545

546

AMERICAN HEART JOURNAL

METHOD OR INVESTIGATION

During the two and one-half years covered bj- this report, seventeen general
hospitals functioned in this Theater. At the time the final data were assembled,
six of these hospitals had been transferred to France and information concerning
their experience with rheumatic fever and rheumatic heart disease before leaving
this Theater was obtained from the chief of the medical service of each by letter.
In another instance (the 26th General Hospital), all records covering their
sojourn in North Africa were destrot’ed by enemy action, but data on the Italian
campaign were obtained from them through the chief of the medical service.
The remaining ten general hospitals in operation in Italy were visited by me and
their records were reviewed. In this fashion complete historical and clinical
data were obtained on 841 individuals with rheumatic fever and/or rheumatic
heart disease. This group of personally reviewed cases comprises the most
valuable source of information in the study and serves as an index of the clinical
features of the disease as it occurred in the United States Army in North Africa
and Italy.

Next in importance is a smaller series of 100 patients included in the afore-
mentioned group which I, in anticipation of a separate clinical report in col-
laboration with Captain Marlow B. Harrison, Medical Corps, studied at the 6th
General Hospital. In this group we were especially interested in the antecedent
historj'- in regard to previous knowledge of heart disease from examinations at
school, for insurance, for industrial employment, or for entrance into other
branches of the service previous to their final acceptance by the Army, as well
as their later experiences in medical establishments after entry into the service.
This carefully questioned group, relative small though it is, serves as our principal
check on the efficiency and thoroughness of induction examinations.

An additional source of data with reference to the incidence of asympto-
matic and unsuspected rheumatic heart disease has been the records of the three
medical laboratories to which protocols, as well as sections of tissue of all post-
mortem examinations in this Theater, were sent for review and confirmation.
Thus the records of the 2nd Medical Laboratory and of the 15th Medical General
Laboratory’' have been studied, and from the 4th Medical Laboratory now in
France pertinent data were received by letter. In this fashion 1,507 consecutive
post-mortem examinations were available for our purpose.

To supplement this factual data, conferences were held with numerous
individuals especially interested or experienced in this field at the headquarters
of the Mediterranean Theater of Operations and of the 5th Army, and in the
general, station, evacuation, and convalescent hospitals. As a result of these
discussions there was agreement that rheumatic fever had been relatively infre-
quent, that rheumatic heart disease in the majority clearly antedated entry into
the service, and, finally, that by limiting this survey to the general hospital,
fully 95 per cent of patients with these conditions would be included. The re-
maining 5 per cent (estimated) would include the occasional patient who, con-
trary^ to the established policy in the Theater, was not referred to a general hos-

bland: rheumatic fever and rheumatic heart disease in u. s. army 547

pital for appraisal, as well as a relatively small number of patients sent directly
to the Zone of Interior by station or evacuation hospitals functioning tempo-
rarily in the role of a general hospital in newly occupied ports prior to the arrival
of the latter. This was the case with the 8th Evacuation Hospital in Casablanca
before the arrival of the 6th General Hospital, and, in like manner, of the 7th
Station Hospital in Oran and the 52nd and 118th Station Hospitals in Naples.
It is our belief, however, that the number of cases escaping attention in this
fashion is negligible.

INCIDENCE

Clinical Data . — ^The over-all clinical data as to incidence assembled from
the general hospitals for the two and one-half year period from November, 1942,
to May, 1945, is summarized in Table I. In analj^zing Table I, it should be
remembered that in the process of evacuation a single patient may have been

Table I. Incidence and Disposition of Rheumatic Fever and/or Rheumatic Heart
Disease in the General Hospitals in the MediterR;\nean Theater of
Operations, United States Army (November, 1942, to May, 1945)

GENERAL

HOSPITALS

TOTAL

DISPOSITIONS

CASES

ZONE OF INTERIOR

LIMITED SERVICE

DUTY

3rd*

6th ;

183

169 (92.3%)

8 (4.3%)

6 (3.4%)

28 (15.7%)

12th

178

135 (75.8%)

15 (8.5%)

17th i

96

91 (94.8%)

2 (2.1%)

3 (3.1%)

2Ist

85

72 (85.5%)

11 (13.0%)

2 (1.5%)

23rd*

24th

40

28 (70.0%)

7 (17.5%)

5 (12.5%)

26tht

44

.33 (75.0%)

0

11 (25.0%)

4 (5.7%)

33rd

70

59 (84.3%)

7 (10.0%)

36th

49

46 (93.8%)

0

3 (6.2%)

37th

34

23 (67.6%)

7 (20-6%)

4 (11.8%)

43rd

58

56 (96.5%)

2 (3.5%)

0

45th

134

134 (100.0%)

0

0

46th

58

1 56 (96.6%)

i 1 (1.7%)

1 (1.7%)

64th

30

29 (96.6%)

1 (3.4%)

0

70th

109

95 (87.1%)

■ 8 (7.3%)

6 (5.6%)

300th

33

27 (81.8%)

4 (12.1%)

2 (6.1%)

Total

1,201

1,053 (87.6%)

73 (6.1%)

75 (6.3%)

♦Information requested but not received at time of submission,
tincludes Italy only (see test).

hospitalized in more than one institution; hence, there is an estimated 10 per
cent reduplication in these figures, which, however, it was possible to correct in
the personally reviewed series of 841 cases which forms the basis of the clinical
discussion later. The reduplication noted accounts in part for the dispropor-
tionately large number of cases from the 6th, 12th, and 45th General Hospitals,
located, as they were, in or near ports of embarkation. An additional factor in
connection with these three hospitals was their relatively early arrival and long

548

AMERICAN HEART JOURNAL

sojourn in the Theater. With due consideration for the various modifying factors
in the available statistics, there were approximately 1,400 patients in the Mediter-
ranean Theater of Operations with rheumatic fever and/or rheumatic heart
disease.

Posl-Morleni Data . — The post-mortem material available for study in this
connection consists of protocols of 1,507 consecutive autopsies from the records
of the 15th Medical General Laboratory and from the 2nd and the 4th Medical
Laboratories. Reference has been made to these records in an attempt to arrive
at some general idea of the incidence of presumably unsuspected rheumatic
heart disease in the Army. As one might expect, the apparent incidence from
these figures is low because they are weighted by the fact that most patients in
whom valvular heart disease is discovered incidentally during hospitalization
for other diseases or injuries are returned to the Zone of the Interior. However,
in this series of 1,507 examined patients, there were fifteen instances of rheumatic
heart disease in Army personnel, an incidence of 9.9 per 1,000. In thirteen of
these fifteen, all of whom died of conditions unrelated to the heart, there were
old well-healed lesions of mild degree, involving the aortic valve in two and the
mitral valve in eleven. The remaining two patients had active rheumatic
carditis. One of these is of considerable interest. This patient, 20 years of age,
had pneumonia complicated by a lung abscess. During the course of the illness
he developed acute migratory polyarthritis typical of rheumatic fever, a persistent
tachycardia, and a loud apical systolic murmur which appeared while he was
under observation. In the course of the illness he received five transfusions of
whole blood. Following the last transfusion he developed icterus, anuria, and
azotemia and died of renal failure. At post-mortem examination the heart
weighed 350 grams. The endocardium of the mitral valve showed hemorrhagic
areas and small linear verrucous vegetations along the line of closure typical of
acute rheumatic endocarditis. Sections of the myocardium also revealed a wide-
spread acute process with edema of the interstitial tissue, mild cloudy swelling
of the muscle fibers, areas of hyperemia, and multiple small hemorrhagic foci.
Sections of the mitral leaflet showed recent hemorrhagic infiltration together with
diffuse infiltration by lymphocytes, plasma cells, and other mononuclear cells.
No bacterial organisms were present in the vegetations. This case represents an
initial acute attack of rheumatic fever complicating lung sepsis and a fatal trans-
fusion reaction.

In connection with the post-mortem incidence of 0.9 per cent noted in this
series, although the figures are not strictly comparable, it is interesting that
Clawson reported an incidence of 2.8 per cent for rheumatic heart disease in
30,265 autopsies in Minnesota^ and that Scott and Gar^’in in Cleveland found
1.7 per cent in 6,548 autopsies.®

Discussion . — Since rheumatic fever was included among the reportable
diseases in this Theater, it is of some interest in the light of this survey to com-
pare our findings with the number of cases formallj' reported to the Department
of Prev'cntable Diseases. It should be noted that our figures discussed in the

BLAND : RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE IN U. S. ARMY • 549

foregoing include both active rheumatic fever and “inactive” rheumatic heart
disease. However, from the clinically studied group, it will be seen later that
58 per cent of the total number of patients had recognizable rheumatic activity.
This indicates that perhaps 600 or more patients of our composite group had
rheumatic fever.

For comparison with this figure, we consulted the records of the Surgeon’s
Ofhce, Mediterranean Theater of Operations, United States Army,* for the
actual number of cases reported. This information was available for the twenty-
eight months from January, 1943, through April, 1945, and is shown in Table II.
The total of 361 cases indicates, in the light of our study, that approximately
one-half of the cases of rheumatic fever were formally reported as such. It is
of some further interest that only one death is recorded from rheumatic heart
disease and one from subacute bacterial endocarditis. We suspect these mor-
tality data are approximately correct.

Table II. Rheumatic Fever Reported in the Mediterranean Theater of Operations,
United States Army (January, 1943, Through April, 1945)

YEAR

JAN.

i

FEB.

MAR.

APRIL

MAY

JUNE

JULY

!

AUG.

sept.

OCT.

NOV.

DEC.

TOTAL

CASES

1943

6

7

1

7

2

2

9

8

10

10

13

14

89

1944 '

1

11

1

11

20

2

26

18

22

24

18

21

16

22

211

1945

1

13

13

19

1

16

i

1

i

i

61

Total

361

Perhaps the most important single factor in the relatively low incidence of
rheumatic fever in this Theater has been the absence in epidemic proportions
of streptococcal sore throats and upper respiratory infections in general among
the troops in this area. According to the records of the Surgeon’s Office, even
minor outbreaks of such were much less frequent than would be anticipated in a
comparable civilian population.

It is of some interest to compare these figures on incidence with those avail-
able for the overseas forces in World War I (1917-1918). Tables III and IV
have been compiled from information contained in The Medical Deparlment of
the United States Army in the World War^ from the section on Admissions in
Europe of White Enlisted Men From April 1, 1917, Through December 31, 1919.
It is to be remembered that the number of troops upon which these figures are
based probably far exceeded the number involved in the Mediterranean Theater
of Operations. Furthermore, the accuracy %vith which the diagnoses of rheu-
matic fever and of r'alvular heart disease were made twenty-five years ago was
considerably less than at present. It is reasonable to suspect that many cases of

*Wo are indebted to Colonel W. S. Stone, Department of Preventive Medicine, for thi.'! information.

550

AMERICAN HEART JOURNAL

Other now well-recognized types of arthritis and allied conditions were included
alone with rheumatic fever in the group labelled “acute articular rheumatism.”
Also, the high incidence of “mitral insufficiency” as shown in Table III suggests
that the significance of systolic murmurs at the cardiac apex was overemphasized.
In spite of these and other equally obvious discrepancies, the striking disporpor-
tion in incidence of these conditions in World War I as compared with this sample
wf incidence in World \A'ar II speaks well for the thoroughness with which sub-
with rheumatic fever and those with long-standing vahnilar disease have
been excluded from the overseas forces.

Table III. Admissions in Europe or White Enlisted Men
(April 1, 1917, to Dec. 31, 1919) (Absolute Numbers)

Acute articular rheumatism

5,745

t’alvular diseases of the heart

2,122

1. Aortic insufficiency

‘ 144

2. Aortic stenosis

28

3. Mitral insufficiency

1,418

4. Mitral stenosis

241

5. Combined lesionc, mitral and aortic

44

6. Tricuspid lesions

3

7. Valvular lesions, unclassified

244

Total admissions (Medical diseases) 702,780

Table IV. Deaths in Europe or White Enlisted Men
(April 1, 1917, to Dec. 31, 1919) (Absolute Numbers)

Acute articular rheumatism 19

Valvular disease of the heart 50

Total deaths (Medical diseases) 29,272

CLINICAL FEATURES

The data which form the basis of the following observations consist of the
group of 841 patients whose hospital records and board proceedings were per-
sonally re\newed. This represents more than one-half of the total number of
known cases in the Theater and hence serves as a reliable index of the main
features of rheumatic fever and rheumatic heart disease under wartime condi-
tions in this part of the world.

These cases fall into two main groups (Table V): I, those patients with
active rheumatic fever and, II, those with the physical signs of valvular heart
disease (rheumatic type) but without demonstrable rheumatic infection.

Active Rheumatic Fever . — ^There were 488 patients, 58 per cent of the series
with clinical or laboratory' eWdcnce of active rheumatic fever. In one-half
(246 patients) it represented a recurrence or reactivation of previously known

BLAND : RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE IN U. S. ARMY 551

Table V. Incidence of Rheumatic Fever and of Rheumatic Heart Disease

(841 Cases Personally Reviewed)

I Active rheumatic fever 488 cases (58.0%)

(a) Rheumatic heart disease 247 (50.6%)

(b) Potential rheumatic heart disease 241 (49,4%)

II Rheumatic heart disease (Inactive) 353 cases (42,0%)

Total rheumatic heart disease 600 cases (71.3%)

infection. In the remainder (242 patients) the present illness appeared to be
the initial onset of rheumatic infection in so far as could be determined from the
history and from the degree of valvular disease present in those with this com-
plication. The presence of well-marked mitral stenosis, for example, was con-
sidered evidence of past rheumatic fever, even though there was no suggestion
of such in the history. In this group of 242 patients whose illness originated
overseas, no clues were apparent to foretell their rheumatic susceptibility. In
view of this it was of some interest to inquire into the immediate circumstances
which may have been a factor in initiating the illness. In civilian experience
it has been repeatedly shown that by far the most frequent event occurring just
before, or concurrently with, the onset of rheumatic fever is streptococcal infec-
tion of the upper respiratory tract. Occasionally, however, other episodes,
nonspecific in character, may apparently act in a similar fashion, especially in
regard to recrudescences of the disease. In this connection and limiting the
observations to the group of 242 patients with “primary” rheumatic fever, it is
noteworthy that the following events occurred with sufficiently striking relation-
ship to the onset to have been recorded in the routine histories of eighty-eight
patients; namely, sore throat (sixty-five instances), injury (ten), severe exposure
(five), malaria (three), acute gastronenteritis (two), phlebitis (one), pneumonia
(one), and lymphocytic meningitis (one). Likewise, in an appraisal of the
precipitating events in the recurrent cases of rheumatic fever, sore throat, injury,
severe exposure, and occasionally malaria occurred in approximately the same
proportion as the foregoing.

The physical findings in 102 patients (42 per cent) of the group with newly
acquired rheumatic fever indicated cardiac involvement, usually of father mild
degree, as would be expected at this age; the majority were in the second decade
of life. The remaining 140 patients showed no pln'^sical signs of cardiac invoh'e-
ment.

There remain 246 patients in the active rheumatic fever group whose illness
represented a recurrence of pre\'iously known rheumatic infection. This ratio
is in accord with the well-known tendency of the disease to recur, especially
under the adverse circumstances of exposure and infection. From the point of
view of the Army, our chief interest in scrutinizing this group has been to evaluate
certain clues which might have been helpful in excluding them from foreign
service. First, 106 of this group had chronic valvular heart disease antedating

552

AMERICAN HEART JOURNAL

their military service and known to the patients as a result of premilitary exami-
nations. Certainh'- in the majority this should have been promptly suspected
by history and recognized by physical examination either at the time of induction
or during subsequent e.xaminations in the service. Second, a review of the
rheumatic fever history of this group is enlightening in that in addition to the
o\'erseas illness, thirty-five of these patients (of whom twenty-one also had
rheumatic heart disease) had had rheumatic fever since entry into the service
and had been treated for it in Army hospitals in the United States. Notwith-
standing this, they were later dispatched overseas, the majority with combat
units. In one extraordinary (and we believe e.xceptional) instance a soldier
20 years of age with known rheumatic heart disease since the age of 12 years
was treated three weeks for severe acute rheumatic fever and well-marked chronic
valvular heart disease of both the aortic and mitral valves at a station hospital
while staging in one of the largest camps in the New York area. Presumably
because of pressure from his unit, this soldier was discharged from the hospital
in order to accompany his organization overseas. He spent the crossing in the
ship’s sick bay and on arrival in North Africa was sent directly to a general
hospital where he continued to exhibit both clinical and laboratory evidence of
rheumatic fever. He was returned promptly to the Zone of the Interior. We
have encountered only one other similar instance of a soldier having been allowed
to continue to his overseas destination after having been hospitalized for rheu-
matic fever at the staging area prior to embarkation. The foregoing represents
the ultimate in mismanagement of these cases; nevertheless, lesser degrees of
such have occurred sufficient^ often to warrant emphasis at this time.

Further inquiry into the history of this group revealed that twelve additional
patients (seven with known rheumatic heart disease) had had previous rheumatic
fever within one year of entry into service, nine patients (five with rheumatic
heart disease) had had previous rheumatic fever within two years of entry into
service, and sixty others (forti'-six with rheumatic heart disease) had given a
history of two or more, and, in some instances, as many as six, previous attacks
of rheumatic fever. It seems to us, at least in retrospect, that in the majority
of these patients their susceptibilit)'’ to rheumatic fever should have been recog-
nized by history and by physical examination at some stage in their military
career prior to their arrival overseas, even though it escaped detection at the
time of induction. At least the thirty-five who were actually hospitalized for
rheumatic fever in military installations in the United States should have been
removed from units destined for foreign service.

The severity of rheumatic fever as it has occurred overseas has been of a
mild to moderate degree in the majority of cases. Acute migratory polyarthritis
responding to salicylate therapy has been the most frequent clinical feature.
Relatively few have shown the manifestations often encountered with the more
severe forms of rheumatic fever, especially as seen in childhood. Of these more
serious manifestations, congestive heart failure occurred in four, pericarditis
in eleven, pleuritis associated with pericarditis in four, pneumonitis associated

BLAND : RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE IN U. S. ARMY 553

with Other signs of severe rheumatic fever including a delayed auriculo\'entricuiar
conduction time of 0,50 second in one, and high-grade heart block of 0.30 second
or more in four patients, one of whom under observation later developed com-
plete auriculoventricular dissociation. One patient 24 years of age e.xhibited
typical rheumatic nodules over the bony prominence of the e.xtremities, and one
other patient, 23 years of age, had a fourth recurrence of typical Sydenham’s
chorea. In no instance was a death from rheumatic fever recorded, although it
was a complicating feature in the patient whose clinical course was briefly noted
in the discussion of post-mortem data in the preceding section.

Rheumatic Heart Disease . — Rheumatic heart disease manifested by the
. characteristic physical signs of valvular deformity was present in 600 patients
(71 per cent) of the clinically analyzed series (Table V). In evaluating the
thoroughness of the screening of Army personnel for the purpose of helpful criti-
cism thereof, it is of interest that 273 (or 45 per cent) of this group had knowledge
of their valvular disease before induction. In the majority (191 patients) this
knowledge was acquired at the time of their childhood rheumatism or at subse-
quent school examinations; in others (thirteen patients), as a result of insurance
or industrial examinations; and b}'- some (twenty-five patients), because they
had been rejected on this account by other branches of the Armed Forces before
their ultimate induction. In eleven instances the presence of heart disease was
recognized at the time of induction but, according to these patients, after con-
siderable discussion and consultation they were accepted. In only two instances
did patients state they were accepted without an examination.

Active rheumatic infection discussed in the preceding section was also present
in 247 of this group and largely determined the management and disposition of
these patients (Table V). There remained, however, 353 patients with chronic
valvular disease of the rheumatic type without clinical or laboratory evidence
of concurrent rheumatic fever. This group with so-called inactive rheumatic
heart disease consisted of those who were hospitalized because of symptoms
directly referable to the heart (in 228 instances) and those whose heart disease
was recognized as an incidental finding during hospitalization for other unrelated
disease or injury (in 125 instances).

The extent of involvement of the heart in 600 patients whose records were
available for review is indicated in Table VI. Cardiac enlargement was present
. in 162 patients (27 per cent). In the majority it was of slight to moderate degree.
Valvular disease in this group differed in no significant fashion from that observed
in similar series for this age group in civilian practice. For example, in a series
of 1,097 patients in New England (White and Jones) in whom \'alvular disease
was sufficient or definite enough to be diagnosed clinically, 56.3 per cent were
thought to have mitral valve disease alone as compared with 69 per cent for the
present series, 14.7 per cent aortic alone as compared with 12 per cent, and 28.9
per cent both aortic and mitral as compared with 19 per cent here.^ The relative
incidences of uncomplicated mitral stenosis and of slight aortic regurgitation
are a trifle greater in this group than is ordinaril}' encountered, and in like fashion

554

AMERICAN HEART JOURNAL

T.irn.r. \'L R}u:vu\ric Hc.irt Discasc (Extcst

or I.VVOIA’C.MC.N'T IN

600 Patients)

Cornhificd ic-ion*;, mitral and aortic

112 (19%)

.Mitral involvement

419 (69%)

(a) Rcftiirgitafiofi and stenosis

J74

ib) Regurgitation

145

(c) Stenosis

100

Aortic involvement

69 (12%)

fa) Regurgitation (Slight)

41

(1)5 Regurgitation (Free)

12

(r) Regurgitation and stenosis

16

combined lesions of the aortic and mitral valves occurred less frequently than is
commonly noted in similar studies. The explanation for these slight discrepancies
%ve believe is evident. In the first instance it is well to remember that the diastolic
murmur characteristic of mitral stenosis is notoriously difficult to recognize by
the inexpert, especially if the patient is not examined recumbent and after
exerci.se. Likewise, the soft blowing diastolic murmur best lieard along the left
.sternal border indicati\-e of slight aortic regurgitation is easily overlooked. It is
to be e.xpecled then that the number of patients with these two isolated lesions
which most easilj- escape detection in hurried examinations would appear rela-
tively more frequently in the group under consideration. Contrariwise, combined
valvular lesions are more easily delected and thus the majority should have
been eliminated from this series. No instance of tricuspid or of pulmonary valve
disease was recognized, and because of their relative rarity it is unlikely that
such have. occurred.

There remain the 241 patients in the active rheumatic fever group whose
heart escaped demonstrable damage (Table V). These are classified as having
potential rheumatic heart di.sease and require no special comment at this time.
It i.s of passing interest, however, that 23 of this group had abnormally long
auriculoventricular conduction times of 0.20 second or more by electrocardiogram
during their rheumatic fever. In one instance the P-R interval measured 0.30
second. It is to be expected that approximately 25 per cent of this group in
the course of months or years will show signs of valvular heart disease.^

Cflmplirations . — The more serious complications of rheumatic heart disease
are auricular fibrillation, congestive failure, embolism, and subacute bacterial
endocarditis. The period of overseas hospital obsen'ation of the patients in the
present seric.s i.^; relatively short, averaging from one to two months, and the
majority of the cases represent relatively mild degrees of heart disease as com-
pared with the usual hospital series in civilian practice. Therefore the incidence
of the.-e important complications would naturally be low.

Auricular uhrillalion was present in eight patients, all of whom had extensive
rheumatic heart disease with well-marked mitral stenosis. In none was activ'e

555

bland: rheumatic fever and rheumatic heart disease in u. s. arjiy

rheumatic fever a factor in precipitating the arrhythmia, and in three instances
it vas paroxysmal in nature. An additional patient with severe rheumatic heart
disease had occasional episodes of paroxysmal auricular tachycardia.

Congestive heart faihire occurred in only three patients. It was precipitated
by a recurrent episode of rheumatic fever in two instances similar in this resp.ect
to the relationship commonly obser\^ed in childhood. The third patient was 44
years of age and had been in the Army for twenty-five years. He had well-
marked cardiac enlargement Avith regurgitation and stenosis of both the mitral
and aortic valves, undoubtedly of many years’ standing. He denied knowledge
of existing heart disease. The onset of auricular fibrillation precipitated con-
gestive failure which responded satisfactorily to rest, digitalis, and diuretics.
Acute pulmonary edema, the result of flooding of the lungs behind a tight mitral
stenosis, so commonl}' observed in severe rheumatic heart disease in civilian
practice, was not encountered in this series.

Embolus from the heart (dilated left auricle) to the peripheral circulation
occurred in three patients, all of Avhom had high-grade mitral stenosis and
auricular fibrillation. In the first instance, a soldier, 35 years of age, with known
rheumatic heart disease since the age of 22, was brought to the hospital with
hemiplegia. The second Avas a soldier 25 years of age with hemiplegia and
aphasia. The third Avas a soldier 48 years of age AAUth eight years’ service, in
AA'hom the onset of auricular fibrillation Avas folloAA'ed in a feAA^ days by an embolus
to the popliteal artery. Pulmonary embolus, AA’-hich may arise from a thrombus
in dilated right heart chambers but most often comes from a thrombosed vein
in the legs or pehns from A'^enous stasis secondary to heart trouble, AA’^as not
encountered in this series.

Subacute bacterial endocarditis occurred in four patients AA'ith chronic rheu-
matic heart disease. In all instances the causatiA^e organism AA'as the Strepto-
coccus viridans. Taa^o of these patients succumbed in this Theater before they
could be eA^acuated to the Zone of the Interior. Post-mortem examination con-
firmed the clinical diagnosis in each. The remaining tAA-o patients Avhose illness
had been present for appro.ximately one month w^ere transferred to the United
States.

Angina pectoris Avas present in three patients 26, 29, and 44 years of age,
respectively, each of AA^hom had free aortic regurgitation. It is of interest that
the eldest member of this group had been in the serAuce for tAventy-tA\m years and
had, in addition to aortic regurgitation, AA^ell-marked mitral stenosis and regurgi-
tation.

Cardiac neurosis a 7 id neurocirculatory asthenia AA'ith predominant cardiac
symptoms are notoriously common in combat troops. KnoAA'ledge of the presence
of a cardiac murmur, no matter hoAV innocuous the latter may be, often serA^es
as the focus of a disabling neurosis. In the patients of this series AAuth rheumatic
heart disease, there AA'ere thirty-eight AA'ith disabling neuropsychiatric disorders.
In seA'-enteen of these, the symptoms AA'ere largely referred to organs of the body

556

AMERICAN HEART JOURNAL

Other than the heart. In the remaining twenty-one, however, the complaints
were those of neurocirculatory asthenia in eleven, and more clearly of cardiac
neurosis in ten. In none of these was the nature or e.N:tent of the valvular disease
sufficient to cause symptoms per se.

DISPOSITION

It was the established policy in this Theater that patients with rheumatic
fever be returned to the United States. In the course of the present survey,
certain deviations from this general rule have been noted in occasional instances,
and the follow-up data indicate a sufficiently high incidence of recurrent attacks
in those who, for one reason or another, were not evacuated to the Zone of the
Interior to support amply the wisdom of the basic recommendation both for the
welfare of the patient and the best interests of the Army. In regard to chronic
\^alvuiar heart disease without active rheumatic fever, the policy was slightly
more elastic in that those with minimal lesions and no cardiac symptoms were,
in some instances, retained in the Theater, usually in a limited service capacity,
and, under special circumstances, were even returned to full duty. In Table I
we have included the disposition figures for the composite group of patients
(those with rheumatic fever and rheumatic heart disease) from the general
hospitals. It will be noted that S7.6 per cent were returned to the Zone of the
Interior, 6.1 per cent were reclassified for limited service and retained in the
Theater, and the remaining 6.3 per cent were returned to full duty. As is evident
from Table I, the disposition policy of the various hospitals varied slightly from
one e.\treme. illustrated by that of the 45th General Hospital, where all patients
with either rheumatic fever or inactive rheumatic heart disease were automaticallj'
returned to the United States to another, illustrated by that of the 37th General
Hospital, where only 67.6 per cent were returned to the Zone of the Interior.
There was a grand total of 30,193 patients boarded for the Zone of the Interior
from the medical sendee of the general hospitals listed in Table I. This figure
includes all neuropsychiatric patients as well as a few with primarily surgical
conditions. In spite of the distortion due to the factors noted in the foregoing,
rheumatic fever and rheumatic heart disease accounted for 3.9 per cent of the
total. f

Disposition of the 353 patients with inactive rheumatic heart disease from
the personally re\'iewed series was as follows: to the Zone of the Interior, 273
paticnl.s (77 per cent): to limited service, foetj^-nine patients (12 per cent); and
to full dut 3 % thirt\’’-one patients (11 per cent). Those who were returned to full
duty had vciy mild valvular lesions which were discovered incidentally during
hospitalization for unrelated disease or injurj', and in the majoritj' of those
assigned to limited servdee, the cardiac findings were minimal and not the limit-
ing factor. There is no evidence, in so far as this studj'^ is concerned, that harmful
cffecLs have resulted in this small group of patients with minimal and inactive
x'alvular disease as a result of their retention overseas. Nevertheless it was
recognized that they were potential candidates for recurrent rheumatic fever and,
to a lesser e.\*tent. for bacterial endocarditis.

BLAND : RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE IN U. S. ARMY

557

CONCLUDING REMARKS

The line of duty status for this group of patients is of importance, for a
considerable number may be expected with the passage of years to become cardiac
invalids. In this connection there has been considerable variation in the criteria
adopted by the different hospitals. In general, however, for those patients who
developed rheumatic fever after entry into the service, irrespective of whether
or not they had had previous attacks, the illness was considered “in line of duty.”
The group of patients with inactive rheumatic heart disease presented a more
difficult problem and the policy of the different hospitals varied considerably
on this score. In the absence of active rheumatic fever and if the histor}’’ revealed
an attack prior to entry into the service, or if the patient had knowledge of the
existence of previous valvular disease, or if the physical signs indicated an ad-
vanced lesion which, from clinical experience, is known to require a minimum of
several years to develop (for example, high-grade mitral stenosis) and the patient's
Army service was of only one to two years, under any of these circumstances
most of the general hospitals considered the valvular disease to have existed
prior to entry into the service, even though it was not noted at the time of induc-
tion and hence was considered not “in line of duty.” Whether or not this decision
will be upheld when the question arises in the future will undoubtedly depend
on the policy adopted at that time by the Veterans’ Administration. The most
difficult situation for a fair appraisal involved those patients Avith a relatively
short Army career who developed acute rheurnatic fever in the service but whose
valvular disease by clinical judgment must have existed for many years. In
these instances the policy followed by most of the hospitals was to consider the
“line of duty” of the rheumatic fever as “yes” and of the advanced valvular
disease as “no.”

In reviewing the data recorded herein and from the personal experience in
this Theater of those especially interested in the problem, as well as from the
available data published from other Theaters,® it is evident that the recommenda-
tions and the measures in force to exclude from overseas service individuals
with chronic valvular disease and those especially susceptible to rheumatic fever
have been highly effective. This conclusion is amply supported by a comparison
with the experience from World War I. ^ That mistakes have occutyed is inevitable
in view of the urgency which total Avar precipitated upon the nation. Our sole
purpose in stressing the more obvious errors AA’^hich in retrospect haA^e come to our
attention is of a constructive nature and can in no Avay detract from the superb
effort and success of all concerned in excluding the majority of these patients
from the Armed Forces.

Finally, and again in retrospect, if all of those AA'ith knoAAm heart disease and
those AA'-ho had had rheumatic fever AAuthin one year of entr}^ into the serAuce had
been excluded, the problem presented to the Army in this Theater AA^ould have
been reduced by 37 per cent. If, in addition, those patients AAdio had a history of
tAVO or more attacks of rheumatic fever had also been excluded, this figure AA^ould
be increased to 43 per cent. This represents perhaps an ideal but impractical
solution in the face of a AA^ar for surAnval.

558

AMERICAN HEART JOURNAL

SmnLARY AXD COXCLUSIONS

A surv^ey has been made of the incidence, clinical features, and disposition
of rlieumatic fever and rheumatic heart disease in Army personnel in the North
African and IMedilerranean Theater of Operations from tlie original landings in
November, 1942, through the Tunisian, Sicilian, and Italian campaigns to the
end of hostilities in May, 1945.

1. Reliable statistical data drawn largely from the experience of the seven-
teen general hospitals in this Theater indicate that approximately 1,400 patients
have been hospitalized, of whom more than one-half had active rheumatic fever
and the remainder, inactive rheumatic heart disease.

2. A review of the protocols of 1,507 consecutive post-mortem examinations
disclosed thirteen instances of healed rheumatic valvular disease of minimal
extent and two instances of active rheumatic carditis, an incidence of -9.9 per
1 . 000 .

3. The clinical features of rheumatic fever and valvular heart disease in a
series of 841 patients whose records were personally reviewed reveals that 58
per cent had active rheumatic infection and the remaining 42 per cent, inactive
valvular disease. The latter was discovered in the majority as an incidental
finding during hospitalization for unrelated disease or injury. The initial onset
of rheumatic fever appeared to have originated in. this Theater in 242 (50 per
cent) of those with active disease.

4. In those in whom valvmlar disease was found, this complication was, in
general, of a mild to moderate degree, and its existence prior to military service
was known to 45 per cent of the group. Of the more serious complications,
auricular fibrillation was present in eight patients, congestive heart failure in
three, embolism in three, and subacute bacterial endocarditis in four.

5. The established policy in this Theater was that all patients with rheu-
matic fever be evacuated to the Zone of the Interior. In regard to inactive rheu-
matic heart disease of minimal degree, the policy was more elastic. In the present
survey it was found that 92.8 per cent of those with rheumatic fever had been
returned to the United States, 3.7 per cent reclassified for limited service, and
3.5 per cent returned to full dut>x Comf)arable figures for those with inactive
rheumatic heart disease were 77 per cent, 12 per cent, and 11 per cent, respec-
tive!}'.

6. Rheumatic fever and rheumatic heart disease accounted for 3.9 per cent
of 30,193 patients boarded for the Zone of the Interior from the medical service
of the general hospitals in the Theater.

7. As a result of this survey, which is supported by published data from
other Theaters, it is evident that the measures now in force to exclude from
foreign service individuals with chronic valvular disease and those especially
susceptible to rheumatic fev'er have been highly effective.

8. In retrospect, if those patients with known heart disease and those who
had had rheumatic fever within one year of entry into the service had been

BLAND: RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE IN U. S. ARMY 559

excluded, the problem presented to the Army in this Theater would have been
reduced by 37 per cent.

The interest and advice of Colonel Perrin H. Long, Medical Consultant to the Surgeon,
Mediterranean Theater of Operations, United States Army, made possible this study. The chiefs
of the medical service of the general hospitals in the Theater rendered invaluable aid by con-
sultation and by letter.

REFERENCES

1. Clawson, B. J.: Incidence of Types of Heart Disease Among 30,265 Autopsies, With

Special Reference to Age and Sex, Am. Heart J. 22: 607, 1941.

2. Scott, R. W., and Garvin, C. F.; Incidence of Tj'pes of Heart Disease Among 6,548 Au-

topsies, With Observations on Race and Sex. Presented before the American Heart
Association, Cleveland, 1941.

3. The Medical Department of the United States Army in the World War, Vol. XV, War

Department, Washington, D. C., 1925, Senate Library.

4. White, P. D., and Jones, T. D.: Heart Disease and Disorders in New England, Am. Heart

J.3: 302, 1928.

5. Bland, E. F., and Jones, T. D.: The Delayed Appearance of Heart Disease After Rheu-

matic Fever, J. A. M. A. 113: 1380, 1939.

6. (a) Sprague, Howard B., and McGinn, Sylvester: Heart Disease and Disorders as Causes

for Evacuation From the South Pacific Combat Area, Am. Heart J. 4: 563, 1944.

(b) Delaney, Joseph H., Miller, Samuel J., Kimbro, R. W., and Bishop, L. F._, Jr.: Valvular
Heart Disease Pfeviouslv Unrecognized in Military Medical E.xaminations, J. A. M.A.
123; 884, 1943.

xorKS ox THE SLMILARITY OF QRS COMPLEX CONFIGURATIONS
IX THE WOLFF-PARKINSON-WHITE SYNDROME

Georgi- E. Burch, M.D., and J. LeRoy Kimball, M.D.

New Orleans, La.

{ X THE W^olff-Parkinson-While sj'ndrome the QRS complexes vary in the
standard leads and have a tendency to repeat their configurations with
I .'tisiderable frequency. It is the purpose of this paper merely to indicate these
\ uious patterns and to give some possible explanations. The significance of
' iic-f variations is not completely understood. It is intended to call to the atten-
iion of others this tendency of the patterns of the QRS' complexes in the Wolff-
I'.irkinson-White syndrome to fall into fairly definite groups so that additional
data concerning them may be accumulated with the idea of better understanding
the nature and significance of the syndrome. Furthermore, the QRS configura-’
tions often resemble electrocardiograms seen in conditions which are of a serious
nature and which may be confused with the less serious Wolff-Parkinson-White
syndrome. Complete left bundle branch block is one serious condition that has
been erroneously diagnosed when the true state was the Wolff-Parkinson-White
syndrome (Fig. 3), It is important that such errors be avoided.

The electrocardiograms available for study in this laboratory and in the
literature re%'iewed‘‘®- contained few precordial leads. For that reason the present
report is limited to the standard leads.

All of the electrocardiograms presented the criteria for the diagnosis of the
Wolff-Parkinson-White syndrome. In summar}'^ these were (1) shortening of
the P-R inter\'al (the P-R segment in particular) and a prolongation of the QRS
duration with slurring and notching; (2) absence of any clinical signs of heart
disease in most instances; (3) occurrence of repeated paro.xysms of tachycardia;
and (4) return of the electrocardiogram to normal on parasympathetic depression
and c.xercise, as well as spontaneously.

For the purpose of this discussion, the features of the configurations of the
QRS complc.xes of the electrocardiograms evident during the period of aberrant
conduction are divided into five types. They are as follows:

Type /. — The QRS complex on first glance appears to be fairly normal.
In Load I the QRS abnormality is limited to the initial portion. It is slurred and
otherwise slightly deformed near the isoelectric line. The QRS comple.xes in
this le.id consist almost entirely of an R wave of great magnitude. The QRS
implex in Lead II shows initial slurring near the base line, while that in Lead III

v tlie Dojinrimont of Modicino, Tulanc University School of Medicine, and Charity Hospital,

xeiv Orleans. L,a.

Received for I'ublicaUon Dec. 17, lOl.'j.

560

BURCH, KIMBALL: QRS COMPLEXES IX WOLFF-PARKINSON -WHITE SYXDROiME 561

is abnormalJy wide but not necessarily slurred or deformed. There may be slight
left-azls deviation (Fig. 1).

Type II. ^There is marked left-axis deviation of the QRS complex. The
QRS complex in Lead I consists mainly of an R wave of great magnitude, while

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562

AMKRia\X HEART JOURNAL

:n Lead III, nn S wave of great magnitude is the conspicuous feature. The QRS
in Ix'.ad II consists of an R and S wave of relatively low but equal amplitude.
Th(‘re is .slurring and various deformations of the QRS complex in Leads I, II,
and ni. Tho.se abnormalities may not be as obvious in Lead II as in the other
kMd.-'. A typical tracing is shown in Fig. 2.

JV!-

B.

I'i:;. S.—Typt' til patlrrn rMcmbUng left bundle braiicli blocK'.

BURCH, ICIMBALL: QRS complexes in WOLFFtPARKINSON- white syndrome 563

Type III . — The pattern of the QRS complex in all standard leads, and,
of course, particularly in Lead I, resembles very closely complete left bundle
branch block. The resemblance to left bundle branch block is so marked that
it is very easy to overlook the syndrome. The short P-R. interval suggests the
correct entity. The QRS complex is slurred and variously deformed throughout
its duration ; the slurring and notching is not limited to the first part of the com-
plex. As in true complete left bundle branch block, the main deflection (the
one of greatest duration) of the QRS complex in Lead I is upright (Fig. 3).

c.

Fig. 3 fCont’d).— For complete legend .see opposite page.

Type IV . — In this type the QRS pattern in Lead I resembles true complete
right bundle branch block. The terminal portion of the QRS complex is an S
wave of great duration. It is this portion of the QRS complex that is especially
slurred and deformed. A slurred R wave of low amplitude in Lead I is usually
present. The QRS complexes in Leads II and III are deformed terminally as
well as initially. There have been only a few such types reported in the litera-
ture, none having been encountered by the authors personally. Fig. 4 is a typical
illustration of this QRS pattern. A case reported by Vakipo appears to be a true
right bundle branch block rather than a Wolff-Parkinson-\ATiite syndrome.

Type F.-^This group consists of QRS patterns of normal duration, in all
three standard leads. The short P-R interval in all leads suggests the correct
syndrome. If patients with such electrocardiograms are followed, subsequent

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I'iS. -1. — Typo IV pattern resembling right bundle brancli block.

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-Typo \ jiatteni with the QKS complexes of normal duration in all leads suggesting essentially
normal order of ventricular depolarization.

BURCH, KIMBALL; QRS COiVIPLEXES IN WOLFF-PARKINSON-WHITE SYNDROME 565

tracings may show the P-R interval to revert to normal and the QRS complex
to alter its configuration simultaneously. The cases reported by Fox'^* and by
OhnelF^ are the only examples of such an electrocardiogram encountered in the
literature. In our personal experience one (questionable) similar electrocardio-
gram was noted (Fig. 5), The second cardiac cycle of Lead III during deep
inspiration (Fig. 5) was initiated by an auricular ectopic focus. This resulted
in a normal P-R interval and a change in the order of ventricular depolarization
indicated by the change iii the QRS comple.x to a more normal appearance.
This is in support of the Wolff-Parkinson-White syndrome. Although the QRS
Comple.x in this fifth type is of normal duration, it may or may not be recognizably
deformed. When there are only slight changes in the order of ventricular depolar-
ization and the resulting deformity is minimal, this slight deformity is earily rec-
ognized when the mechanism reverts to normal and the normal QRS complex
becomes apparent.

DISCUSSION

It is generally agreed that the Wolff-Parkinson-White syndrome is produced
by an anomalous connection (cardiac muscle or neuromuscular pathway) between
the atria and the ventricles.®’®’ “ This results in an early activation of ventricular
depolarization. The order of depolarization begins, at least, in an abnormal
fashion. The site of initiation is determined by the site of connection of the
anomalous pathway to the ventricle. As far as the initiation of ventricular de-
polarization is concerned, the net result is similar to the initiation of ventricular
depolarization by an impulse originating in an ectopic focus in the ventricular
musculature as in ventricular ectopic beats. In the case of ventricular premature
contractions, ventricular depolarization is not completed by an impulse entering
the Purkinje system later from the atrioventricular node as is the case in the
Wolff-Parkinson-White syndrome. It is well to remember that combination
complexes (QRS) may even resemble those of the Wolff-Parkinson-White
syndrome if an ectopic focus in the ventricles initiates ventricular depolarization
late in the cardiac cycle and the normal impulse from the auricle enters the
ventricle from above via the normal pathways to complete ventricular depolariza-
tion. The number of sites of origin of ventricular depolarization in ventricular
premature contractions is unlimited, and the resultant variations in configurations
in the recorded QRS complexes are likewise unlimited. This is essentially true
also for the Wolff-Parkinson-White syndrome. However, in this syndrome,
because of the nature of the anomalous pathway, the ventricular terminus
(anatomic and electrical) is near the base of the ventricle (it is quite unlikely,
though conceivably possible, for the anatomic and electric terminus to be near
the apex of the heart). For that reason the initial process of ventricular depolar-
ization in the Wolff-Parkinson-White syndrome should resemble in all respects
the initial process of a ventricular premature beat initiated by an ectopic focus
located in the base of the ventricle which is the site of termination of the anomalous
pathways. The records in the completed electrocardiograms should resemble
each other.

566

AMERICAN' HEART JOURNAL

Tfic* order of depolarization and the configuration of the QRS in the com-
pieu'd elecirorardiogram is also influenced by the relation of the site of termina-
rimi of the anomalous pathway to the epicardial and endocardial surfaces.

From tite foregoing discussion, it is obvious that the QRS patterns in the
W oltf-Parkinson-W hite syndrome should bear a relation to the QRS patterns
ill veiuricuiar premature contractions. If the anomalous pathway ends in the
nJii M-ntricle, the initial slurred portion of the QRS complex is upright in
Lead 1 In the studies of Rosenbaum and associates^ the slurred abnormal por-
tion of the QRS complex in Lead I was found to be upright and the anomalous
patlmay was found to terminate in the base of the heart more in the right half
of the muscle mass. \\’ood and Wolferth’® were fortunate enough to study
hi-toiogically the heart of a patient who in life had an eledtrocardiogram pre-
tinting the Wolfl-Parkinson-White syndrome. The slurred and deformed por-
tion of the QRS in Lead I was upright and the serial sections of the heart show^ed
llie anomalous patlnvay to terminate in the base of the right ventricle. OhnelP^
ai'-o found an anomalous band of muscle connecting the left atrium to the left
M-ntricle near the interventricular septum. The electrocardiogram, as would
be expected, resembled that of Type V discussed.

The fact that the QRS configurations in the Wolff-Parkinson-White syn-
drome fall into five types ma}' be fortuitious in view of the fact that there are
not many such cases available for analysis. It is quite possible, however,
for the site of termination of the pathways to be fairly constant. Not until
many electrocardiograms and much autopsy material have been accumulated
will this be understood.

The configurations of the QRS depend upon the order of ventricular depolar-
ization. In the Wolff-Parkinson-White syndrome the QRS complex is essen-
tially a combination complex, as mentioned previously. There is a force of
depolarization produced bj'^ a depolarization process initiated in the ventricles
at the terminus of the anomalous pathway and another force of depolarization
produced by a depolarization process in the ventricles initiated in a normal
fashion in the remaining polarized resting muscle by an impulse reaching the
ventricle via the A-V node and Purkinje system. It is obvious that the relative
times of initiation and duration of these two processes of depolarization will
influence the qualities of the forces involved and the configuration of the QRS
complexes in the completed electrocardiogram. For example, if an anomalous
pathway terminates in the base of the right ventricle, an impulse entering this
pathway will initiate depolarization of the right ventricle. Because of the posi-
tion of this ventricle in relation to the right-arm and left-arm electrodes of Lead I,
an abnormally shaped QRS complex wflth relatively small manifest magnitude
IS in^crihed in the completed electrocardiogram. Should the A-V node delay the
normally progressing impulse from the S-A node for 0.15 or 0.16 second, sufficient
time will have elapsed for practically all of the free wall of the right ventricle
anc most of the septum completel}'^ to be depolarized by the aberrant impulse,
i ow . w len the normal impulse enters the ventricle, the depolarization process

BURCH, KIMBALL: QRS COMPLEXES IN WOLFF-PARKINSON-WHITE SYNDROME 567

is not only completed in a more or less normal fashion, but a marked left-axis
(mean) deviation of the QRS complex results. This marked left-axis deviation
is to be expected since the electromotive force created by the depolarization
process in the left ventricle exists almost alone or alone; that is, free from
any neutralizing influences by forces of depolarization in the right ventricle
which has already been depolarized from the anomalous pathway. Because
of the mass of muscle in the left ventricle and the position of the wall of this
ventricle in relation to the right-arm and left-arm electrodes of Lead I, the
manifest magnitude of the QRS axis is great terminally. This reasoning offers
an explanation for the Type II QRS complexes (Fig. 2). A study of the cases
reported in the literature in which electrocardiograms were taken with and
without conduction through the anomalous pathways support the foregoing
explanation.*’'

In the Type I (Fig. 1) QRS pattern, the delay of the impulse from the auricles
b}'^ the A-V node must be relatively short (about 0.15 second in most instances)
so that the process of ventricular depolarization initiated via the anomalous
pathway is of relatively short duration; under these circumstances most of ven-
tricular depolarization is initiated via the impulse from the A-V node. From
a study of the cases with and without function of the anomalous pathway reported
in the literature, this appears to be true.^"®

This same argument can explain the QRS conhgurations of Types III and
IV (Figs. 3 and 4). In order for the slurring and various types of deformities
in the QRS complexes to occur throughout or almost throughout the duration
of the QRS complex, the depolarization process initiated at the terminus of the
anomalous pathway must progress through all or most of the ventricles un-
influenced by another depolarization process initiated by an impulse traveling in
a normal fashion via the A-V node. This would occur if the A-V node conduction
at the time were relatively slow, 0.18 second or longer. The influences of
digitalis^^ in delaying A-V conduction and increasing the duration of the depolar-
ization process initiated via the anomalous pathway is in support of the fore-
going argument. If this be true, the QRS complexes should closely resemble
ventricular premature contractions. Impulses entering the right ventricle via
an anomalous pathway should resemble right ventricular premature contractions.
In fact, the QRS complexes with the main deflections positive in all three standard
leads in Fig. 3 and with the secondary type of T wave changes have the charac-
teristics of right ventricular premature contractions initiated by a focus in the
base of the right ventricle. Similarly, the QRS complexes in Fig. 4 resemble left
ventricular premature contractions.

In support of the idea of relatively delayed A-V conduction explaining
tracings of Types III and IV, Figure 3, A is shown. In this figure the P-R
interval during the normal mechanism is from 0.18 to 0.20 second. When this
time interval is measured after the beginning of the P waves in Fig. 3, it is noted
that an impulse could not have entered the ventricles until they were almost
completely depolarized by means of the then functioning anomalous pathway.
In fact, by 0.18 to 0.20 second from the beginning of the P waves of Fig. 3 the

56K

AMERICAN' heart JOURNAL

\'entncular musculature is so completel}* depolarized that the muscle could
not cvi-n respond to a stimulus that might present itself via the A-V node.
A ■'tudy of tracings of Types III and lY reported in the literature for periods of
functioning and nonfunctioning anomalous pathways showed P-R intervals or
\-\' ilclays which support the foregoing argument.

The imiiortance of timing of the two depolarization processes in Wolff-
1“ rkmson-W'hite syndrome is evident. The marked tendency for A-V node
COP duct ion (P-R interval) to vary in health and disease and under the influence
' >t drugs is well known. In view of the marked variations in the delay of auricular
impulses in the A-V node, it is not surprising that upon this basis alone the QRS
( omplexes in Wolff- Parkinson-White syndrome should be so variable and a QRS
tracing of Type I should change to one of Type III. If the matter of timing
were the only important factor concerned with the production of variations in
the QRS configurations, it would be possible to classify the configurations of the
recorded QRS complexes on relative timings of impulse conduction via the
anomalous and A-V node pathways. There are, however, several other factors of
importance which can influence the configuration of the QRS complexes. The
integration of such factors as anatomic rotation of the heart, multiple pathways
functioning simultaneously or separately which terminate in various portions
of the ventricle, along with variations in delay in A-V conduction, certainly
must contribute to the variations in the QRS pattern from patient to patient or
from moment to moment within the same patient.

From the configuration of the QRS complexes in the standard leads, it
is possible to have only a genera! impression of the site of termination of the
pathways. In Type V (Fig. 5) the QRS complexes are of normal duration and
may or may not be recognizablj' deformed. The rather normal or normal-
appearing QRS complex during the abnormal mechanism indicates a fairly normal
order of ventricular depolarization. For the order of ventricular depolarization
to be about normal, the abnormal pathway must have terminated in the inter-
ventricular septum near its base, in the bundle of His, or in either of the main
branches near the bundle of His. Such an anatomic termination of the anomalous
pathway is quite po.ssible and is a probable explanation for the Type V tracing
(Fig. 5). The finding in Ohnell’s patient of a QRS complex of normal duration
and only slight deformation and on serial section a short (6 mm. in length)
anomalous bundle terminating near the base of the left ventricle near the septum
is certainly in support of the hypothesis presented to explain the Type V tracings.

Irinally, the tcndenc\" for QRS patterns to repeat themselves is pointed out
not for the purpose of recommending that the tracings be so classified for clinical
purposes, but merely to indiatte this tendency in order to lead to a better dis-
cussion and pre.sentation of some of the physiologic concepts of the Wolff-
Parkinson-V hite syndrome. OhnelF' has made an extensive and detailed study
of the various electrocardiographic patterns and has classified them on their
configurations rather than on the electric events responsible for them. Obvi-
ously, if one considers minute details of configurations of the electrocardiograms.

BURCH, KIMBALL: QRS COMPLEXES IN WOLFF-PARKINSON- WHITE SYNDROME 569

the patterns can show unlimited variations. The five general types discussed
reduce the configurations to more practical levels. Minute detailed descriptions
based upon empirical rules seem to add little at this.time.

SUMMARY

1. The tendency of the QRS configurations in Wolff- Parkinson -White
syndrome to fall into five types is pointed out.

2. An analogy between the initiation of ventricular depolarization by the
terminus of the anomalous pathway and a similarly located focus of a ventricular
premature contraction is drawn.

3. An electrocardiogram of a questionable case of Wolff- Parkinson- White
syndrome with normal-appearing QRS complexes is presented in Fig. 5. It
is suggested that these QRS complexes were initiated by impulses reaching the
ventricles via an anamalous pathway terminating in the center of the septum
near its base or in the bundle of His.

4. Theoretic explanations are offered for the QRS patterns observed in
the Wolff-Parkinson-White syndrome.

REFERENCES

Type I

1. Rosenbaum, F. F., Hecht, H. H., Wilson, F. N., and Johnston, F. D.; The Potential Vari-

ations of the Thorax and the Esophagus in Anomalous Atrioventricular Excitation
(WolfF-Parkinson-White Syndrome), Am. Heart J. 29; 281, 1945. (Cases 1 and 4.)

2. Wolff, L., Parkinson, John, White, P. D.: Bundle-Branch Block With Short P-R Inter\'al

in Healthy Young People Prone to Paroxysmal Tachycardia, Am. Heart J. 5: 685,
1930. (Cases 2, 3. 4, 6, 7.)

3. Tung, C.: Functional Bundle-Branch Block, Am. Heart J. 11: 89, 1936. (Case 2.)

4. Wedd, A. M.: Paroxysmal Tachycardia, Arch. Int. Med. 27; 571, 1921. (Case 1.)

5. Pearson, J. R., and VVallace, A. W.: The Syndrome of Paroxysmal Tachycardia With

Short P-R Interval and Prolonged QRS Complex With Report of Two Cases, Ann.
Int. Med. 21; 830, 1944. (Case 2.)

6. Wolferth, C. C., and Wood, F. C.: The Mechanism of Production of Short P-R Interv'als

and Prolonged QRS Complexes in Patients With Presumablv Undamaged Hearts:
Hypothesis of an Accessory Pathway of Auriculo-ventricular Conduction (Bundle of
Kent), Am. Heart J. 8; 297. 1933. (Cases 4 and 9.)

7. Bishop, L. F.: Bundle Branch Block With Short P-R Interval in Individuals Without

Organic Heart Disease, Am. J. M. Sc. 194; 794, 1937. (Case 1.)

8 Kaplan, G., and Cohn, T. D.; Syndrome of Auriculoventricular Accessory Pathway, Ann.
Int. Med. 21: 824, 1944. (Case 2, R. W.)

10 ,

11 .

12 .

Type II

Rosenbaum, F. F., Hecht, H. H., Wilson, F. N., and Johnston, F. D.; The Potential Varia-
tions of the Thorax and the Esophagus in Anomalous Atrioventricular Excitation
(Wolff-Parkinson-White Syndrome), Am. Heart J. 29; 281, 1945. (Case 10.)

Wilson F. N.: A Case in Which the Vagus Influenced the Form of the Ventricular Com-
plex of’the Electrocardiogram, Arch. Int. Med. 16; 1008, 1915. (Case C.)

Riitterworth I. S.,'and Poindexter, C. A.,: Short P-R Interval Associated With a Pro-
longed QRS Complex, Arch. Int. Med. 69; 437, 1942. (Case T. B.)

Wolferth C. C.. and Wood. F. C.: Further Observations on the Mechanism of the Pro-
duction of a Short P-R Inteia^al in Association With Prolongation of the QRS Com-
plex, Am. He.\RT j. 22: 450, 1941. (Case R. M. and Case A. B.)

AMERICAN HEART JOURNAL

570

I ^ WolfT L., Parkinson. J.. and White, P. D.: Bundle-Branch Block With Short P-R Inter\'al
'in Hcalthv Yoiinsr People Prone to Paroxysmal Tachycardia, Am. Hr.\rt J. 5: 685,

19.10. (Cases 1, 3, S, 10.) . « . , • , a -n

14 Kaplan G . and Cohn, T. D.; Syndrome of Aiinculoventncular Accessory Pathway, Ann.
lilt. Med. 21 ; 824, 1944. (Case J. P.)

15. .‘^lelcr, L. IL: Functional Bundle-Branch Block (Partial) Paradoxically Relieved by Vagal
.Stimulation, Am. J. Sc. 18.5: 211, 1933. (Case 1.)

!6 .Movitt, E. R.: Some Obsen'ations on the Svndrome of Short P-R Intenml With Long
QRS, Am. l-lK.tnT J. 29: 78. 1945. (Case W. A.)

17 Ma-ter. A. M.. Joffc, H. L.. and Dack. S.; Atypical Bundle Branch Block With Short P-R
Interval in Graves' Disease, J. Mt. Sinai Hosp. 4: 100, 1937. (Case D. O.)

'..s ! l.tniburger, W. W.; Bundle Branch Block. Four Cases of Intraventricular Block Showing

Sonic Interesting and Unusual Clinical Features, M. Clin. North America 13: 343,
1929. (Case 4.)

I'i .Spangcnberg, J. J., Vedoya, R., and Gonzalez Videla, J.: Un Caso de QRS ancho y. mellado
con PR acortado. Rev. argent, de cardiol. 4; 244, 1937. (Case 1.)

’ll. Wfxxl, F. C., and Y’olferth, C. C.: Histologic Demonstration of Accessory Muscular Con-
nections Between Auricle and Ventricle Short P-R Interval and Prolonged QRS
Complex, .^M. Heart J. 25: 454, 1943. (Case A. F.)

21. Wolfcrlh, C. C., and Wood, F. C.: The Mechanism of Production of Short P-R Intervals
and Prolonged QRS Complexes on Patients With Presumably Undamaged Hearts;
Hvpothesis of an Accessory Pathwav of Auriculoventricular Conduction (Bundle of
Kent), Am. Heart J. 0: 297, 1933. "(Case 1, Fig. 2— Case 7.)

Type III

22. Rosenbaum, F. F., Hecht, H. H., Wilson, F. N., and Johnston, F. D.: The Potential Varia-
tions of the Thorax and the Esophagus in Anomalous Atrioventricular Excitation
(WoKT-Parkinson-Whitc Syndrome), Am. Heart J. 29: 281, 1945. (Case 8, Case 9.)
2.3. Sigler, L. H.; Functional Bundle Branch Block (Partial) Paradoxically Relieved by Vagal
Stimulation, .Am. J. M. Sc. 185: 211, 1933. (Case C. E.)

24. Wolff, L., Parkinson, J., and White, P. D.: The Bundle-Branch Block With Short P-R

Interval in Healthv Young People Prone to. Paro.xysmal Tachycardia, Am. Heart J.
5; 685, 1930. (Case 5.)

25. Hunter, .A., Papp, C., and Parkinson, J.: The Syndrome of Short P-R Intervals, Apparent

Bundle Branch Block and Associated Paroxysmal Tachveardia, Brit. Heart J. 2:
107, 1940. (Case 1.)

26. Lynch, J. P.. and Mc.Allister, R. G.: The Wolff- Parkinson-White Syndrome, Virginia M.

Monthly 70: 415, 1943. (Case R. S.)

27. Roberts, C. H., and .Abramson, D. D.: Ventricular Complexes of the Bundle Branch Block-

tj’pe -Associated With Short P-R Intcrx'als, Ann. Int. Med. 9: 983, 1936. (Case A. N.)

28. Pearson, J . R., and Wallace, A. W.: The Syndrome of Paroxysmal Tachj'cardia With Short

P-R Interval and Prolonged QRS Complex With Report of Two Cases, Ann. Int.
Med. 21: 830, 1944. (Case 1.)

Type IV

20. Tuntr, C.: Functional Bundle-Branch Block, Am. Heart J. 11; 89, 1936. (Case 1.)

30. A^akil, R. J.: A Case of Mitral Stenosis With Apparent Bundle Branch Block, Short P-R
Intervals and .Attacks of Paroxysmal Tachycardia, Indian M. Gaz. 77; 521, 1942.

Type V

31. Fox. T.; Aberrant .Atrio-ventricular Conduction in a Case Showing a Short P-R Interval

and an .Abnormal But Not Prolonged QRS Complex, Am. J. M. Sc. 209; 199, 1945.
(Ca.=c 1.)

32. Authors’ case (Fig. 5).

33. Fox, r .. Travel. J., and Molofsky, L.: Action of Digitalis on Conduction in the Syndrome
,. ff Short P-R Inteix’al and Prolonged QRS Comple.x, Arch. Int. Med. 71; 206, 1943.
uhnell. R. F.: Pre-excitation, .A Cardiac Abnormalitv, Stockholm, 1944, Acta Medica

Scandinavica, Supplement No. 152.

THE SYNDROME OF ABDOMINAL AORTIC ANEURYSM RUPTURING
INTO THE GASTROINTESTINAL TRACT

Summary of the Literature and Case Report

Homer H. Hunt, M.D., and Carl V. Weller, M.D.

Ann Arbor, Mich.

UPTURE of an aneurysm of the abdominal portion of the aorta into the
gastrointestinal tract is accompanied by a characteristic sjmdrome which
will usually suggest the diagnosis. This dramatic accident is sufficiently rare to
justify the continued reporting and collection of cases for analysis. In this paper,
another example of the rupture of such an aneurysm into the duodenum is re-
corded, and the list of reported cases is brought up to date.

Including the one reported here, forty-one cases have now been collected.
Undoubtedly others are concealed in the numerous studies of aortic aneurysm
in general. In 1943, Rottino,^ in a very thorough search, found thirty-one
examples of rupture of an abdominal aortic aneurysm and added a case of his
own. The essential clinical and morphologic data concerning the group, so far
as they were obtainable, were arranged by him in tabular form. Our Table I,
adding nine cases, is purposely constructed as a continuation of that presented
by Rottino, using the same headings and continuing his serial numbering. Since
the cases reported by Nunneley^ and Penas^ were not known to Rottino, his own
case becomes the thirty-fourth in the series. References to the cases in Rottino’s
table will not be repeated except that for Vehling,"* whose dissertation, available
in microfilm, can now be cited more accurately.

Probable examples, which do not qualify for inclusion in Table I because
perforation was impending rather than actual, or because it is not clear that the
aneurysm was primarily aortic, can be found among studies reported from
other points of view. Washburn and Wilbur^ described obstruction of the third
portion of the duodenum by an aneurysm of the abdominal aorta. The patient
was a woman, aged 67, with a large, pulsating, epigastric mass. There had
been no blood in the vomitus, but later there was a slight trace of blood in a test
meal and occult blood in the stools. Rupture must have been impending in
this case. The clinical diagnosis was confirmed Avhen a posterior gastroenter-
ostomy was performed for the relief of obstruction.

In an analysis of the symptoms and signs in a group of twenty-four cases of
abdominal aneurysm, Eliason and McNamee^'' found massive hematemesis and
melena each mentioned once. Although pain was the predominant symptom in

From the Department of Pathology, University of Michigan.

Received for publication April IS, 1946.

571

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five weeks stools with dark red liquid cm. above aortic bi-

feces in bed; death furcation, rupturing
forty minutes later into jejunum 2 cm.

below duodenum

HUNT AND WELLER: RUPTURE OF ABDOMINAL AORTIC ANEURYSM

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’•'Numberwl in sequence with cases collected by Rottinoi

574

AMERICx\X heart journal

thr* i^roijp ns n whole, reference is ni<i<fe to one patient who had a erj little pain
but did imve massive hematemesis from rupture of an aneurysm of the cehac
axis into the jejunum. Death occurred twenty-four hours after the onset of
hemorrhage. This case and one other, attributed to the celiac axis, are excluded
from Table I.

Scott" included lesions of any abdominal artery in his report of ninety-six
ca-es of abdominal aneurj^sm. “Massive gastrointestinal hemorrhage followed
nijilure into the duodenum in one patient.” In his table a second patient is
ri-corcled as having hemorrhage into the duodenum following rupture. Whether
one or both of these were aortic aneurysms is not stated.

A brief account of our case follows.

CASE REPORT

I. B., No. 4S3037, was an unmarried Swedish bricklayer, aged 47. He was adinitted to the
I niversity of Michigan Hospital with a painful left knee as his chief complaint. Physical evi-
drticc.s of septic arthritis were present and bone destruction was found roentgenographically.
The patient developed an acute psychosis and a reliable history could not be obtained. How-
e\cr, he referred the onset of pain to a period about one month prior to admission. Venereal
infection was. denied, but exposure si.x weeks before entry was admitted. Serologic test of the
blood (Kahn) was negative on two occasions. The gonococcal complement fi.xation test of the
blood .scrum was strongly positive. Tlie patient was given sulfathiazolc, and three operative
procedures for drainage of the left knee were carried out. On the third postoperative day, at
5 the patient had a sudden hemorrhage from the mouth, amounting to about 300 c.c. of
fluid and clotted blood. A medical consultant suggested pulmonarj' infarction, but roentgeno-
grams of the chest were negative. None was made of the abdomen. At 10:15 a.m. of the same
d.iy, tlie patient had a second hemorrhage and expired.

Autopsy. — At autopsy (A'420-.‘\S), the. stomach, duodenum, and entire small bowel were
found to be filled with a jellylike blood clot forming a cast of the lumen. In the transverse seg-
ment of the third portion of the duodenum there was a small, irregular opening which communi-
cated with a firm, somewhat clastic, retroperitoneal mass. After removing the duodenum and
aorta together, this mass was found to he a saccular aneurysm protruding from the right antcro-
latcml surface of the abdominal aorta. The sac measured 6 cm. vertically, 4.5 cm. transversely,
and 3.5 cm. ventrodor-sally. Its upper liordcr was 4.5 cm. below the orifice of the superior mesen-
teric artery and it.s lower border 2 cm. above the iliac bifurcation. The mouth of the sac lay to
tile right of the inferior mesenteric artery and measured 2.5 by 2 centimeters. The wall of the
sac was composed of thick fibrous and calcareous laminae (Figs. 1 and 2). The remainder of the
ahdornin.il aorta showed thickening of the wall, loss of elasticity, widening of the lumen, and
numerous j-cllowi.s-h-grny, elevated, hyaline plaques against a grayish-white intima. There were
al.so area.s of atheromatous “ulceration,” but the gross features of syphilitic aortitis were not
found.

Sections of all organs were examined microscopically. The heart showed atherosclerotic
cliangcs of the coronary arteries and at the bases of the aortic cusps. In the myocardium there
Were scattered interstitial infiltrations of mononuclear cells, in part eosinophtles, which were
thought to he due to the u.=e of sulfathiazolc.

1 he aorta was examined in .sections from several levels. In the upper portion of the thoracic
aorta, atheromatous changes were of but slight degree. There was a very moderate increase in
•he blood vessels of the adventitia, about some of which there was a slight lymphocytic infiltra-
tion. In the abdominal aorta there were very marked atheromatous lesions of the intima, with
depo'ition of cholesterol and calcareous plaques. The media showed areas of necrosis with
fnigmeritation and ultimate loss of clastic fibers. In the adventitia there were infiltrations of

Fig. 1. — The abdominal aorta has been opened appro.’dmately along the mid-dorsal line. The
mouth of the aneurysmal sac is showm to the right of tiie opening of the inferior mesenteric artery.
The adherent duodenum is largely concealed by the sac of the aneurysm.

Fig. 2. — This schematic drawing, prepared from a photograph and sketch made at the time of the
autopsy, shows more clearly the anatomic relations of the aneurysm. Rupture into the duodenum
occurred at the summit of the convexity of the anterior wall of the sac.

AMKRICAX HEART JOURNAL

anf! pJn^nn cells, but the changes found were not such as to justify a diagnosis of
■.ypnHitir aurliti'^.

Near t he point of perforation of thcaneurysm into the duodenum there were organizing, fibriii-
icn P'-n'.onit!' ,ind necrosi- ami Icucocjtic infiltration of the mucosa-

A -ection of synovial membrane from the left knee showed active chronic pyogenic inflam-
,'i ition with nmniTOUs p!a~ma cells. This was considered to be fully compatible with the clinical
of gonococcal arthritis.

1 he pathologic diagnoses were: large saccular aneurysm of the abdominal aorta, with rupture
• the third portion of the duodenum and massive hemorrhage into the bowel; hematemesis,
.ivpiration of blood into the lung.s; advanced aortic atherosclerosis; organizing fibrinous
i-Titonitis of the duodenum; coronarr- atherosclerosis; old cpicarditis; subepicardial fatty atrophy
III ita mt oenrdium; left ventricular myocardial hypertrophy; interstitial myocardial infiltrations
•«! I. true mononuclear cells and eosinopliilos (sulfathiazole?); pulmonary congestion and edema;
hi ginning terminal lobular pneumonia; degenerative fatty infiltration of the liver and kidneys;
■ epiic arthritis of the right knee (gonococcal?); cholelithiasis.

DISCUSSION

Incidence as to Sex and Age. — This augmented series adds to the earlier em-
jilmsis upon the greater liability of men to this syndrome. With thirty-five
of forty-one examples in nien,< a 6;1 ratio is found. The range in age remains
unaltered, from 20 to 81 3 ‘ears. While the distribution by decades is fairly uni-
form between these extremes, correction for total number living would show an
increasing incidence beginning with the sixth decade. It can be due onl}' to
chance that for four of the thirty-eight patients the age was 28 years. Yet the
occurrence of eight cases in the six-year period between 27 and 32 years-of-age
emphasizes the importance of this syndrome in a comparatively young group.

Location of the Aortic Aneurysm. — In sixteen cases the level at which the
aortic nneurj’sm had developed was not stated with sufficient e.xactness to be
used in tabulation. IVIoreover, the large size of manj'^ of these aneurj'^sms in
comparison to the small distances between successive aortic branches must have
rendered exact localization impossible in many cases. Locations were specified
as follows; above celiac axis, two cases; at celiac axis, three: above superior
mcscnicric anery, one; at superior mesenteric arterj*, one; below superior mesen-
teric arfery, five; above renal vessels, one; below renal vessels, six; below inferior’
mc.scntcric arter\'. two: lower abdominal aorta, one; above aortic bifurcation,
three.

Location of Rupture Into Gastrointestinal Tract. — As found by Rottino, the
third portion of the duodenum is the portion of the gastrointestinal tract into
which perforation of an abdominal aortic aneurysm occurs most frequenth'.
riiis site was specified, or could be deduced, in twentj'^-nine of the fort^’^-one
aises. In two others, perforation was into the second portion of the duodenum,
and in two into the duodenum, without specification as to the portion. Of the
remaunng cases, five showed perforation into the stomach, two into the jejunum,
and one into the small bowel, with the region unspecified. The reasons for the
preponderance of perforation into the third portion of the duodenum are anatomic,

HUNT AND WELLER; RUPTURE OF ABDOMINAL AORTIC ANEURYSM

577

depending in part upon the extensive area in which this portion of the duodenum
is in relationship to the anterior aortic wall and also upon its firm fixation to the
aorta, since the duodenum is retroperitoneal in this portion.

CLINICAL ^MANIFESTATIONS

The syndrome produced by the rupture of an abdominal aortic aneurysm
into the gastrointestinal tract combines the features of abdominal aneurysms in
general with those of hemorrhage into the alimentary tract. An accurate ante-
mortem diagnosis may be possible in spite of the rarity of the condition.

For the basic clinical picture of abdominal aortic aneurysm, Kampmeier'’
gave the following as important diagnostic points: presence of an abdominal
tumor (60 per cent of all cases) ; expansile pulsation of the tumor (in 98 per cent
of those with tumors) ; roentgenologic evidence of a calcified abdominal mass, of
vertebral erosion, or of an indefinite soft tissue mass (confirming evidence being
found by this method in 75 per cent of thirty-two cases in which it was used).
With any abdominal aortic aneurysm, death is usually due to hemorrhage, whether
the aneurysm is saccular or dissecting. Sometimes death is almost instan-
taneous, but it may be delayed for hours or days. Lipshutz and ChodoflF^®
added to the general picture of abdominal aneurysm the following, as evidence
that rupture had occurred; vascular crisis and a state of shock, a high leucocyte
count, moderate elevation of diastase content of the urine.

All of the diagnostic criteria summarized by Kampmeier and by Lipshutz
and Chodoff apply to the cases of aneurysms in which perforation into the gastro-
intestinal tract is impending or has occurred. The tumor mass is usually epi-
gastric in position and it is frequently expansile and pulsating. Pain is the
chief complaint and may be abdominal or in the lumbar region. Hematemesis
and melena are usual terminal features but, as with thoracic aortic aneurysms,
there may be a premonitory seepage of blood for days or weeks before the final
exsanguinating hemorrhage. This may be discovered through blood-tinged
vomitus or as occult blood in the stools. Death may occur immediately, or after
a variable interval, following the copious hematemesis or escape of fresh blood
from the rectum which completes the diagnostic picture. The report by Manson'^
is typical. "I was called to a passenger train on June 18, 1936, to attend a man
who was seriously ill. This man was found to be lying on his back in a first-
class lavatory with his trousers down, in a mass of blood and feces. He was
blanched and unconscious, and at first sight seemed to be dead.” A pulsating
tumor was felt in the epigastrium. This patient died five days later and was
found to have a saccular aneurysm of the abdominal aorta, which had ruptured
into the duodenum. In our own case, hematemesis marked the occurrence of
rupture.

There are additional features which may lead the clinician away from the
correct diagnosis unless their logical association with this syndrome is recognized.
For instance, a high leucocyte count appears to be a constant feature during
the period between actual rupture and death. Again, a detailed history of “indi-

AMERICAN HEART JOURNAL

STiP

may seem to point so clearly to peptic ulcer that the physical and roent-
penngraphic e^•idences of aneurysm may be overlooked. The frequency with
v.hich an elevated value for urinary diastase will be found has nofj^et been estab-
lished but deserves further study. Impairment of renal function has been ob-
'^erved in many instances and depends chiefl}’" upon interference with one or both
renal arteries. In the case described by Howland and Sprofkin,® in which there
■’ as terminal anuria, the mouths of the renal arteries were included in the an-
eurysmal sac and a thrombus e.\'tended into the right renal artery.

SU.MMARY

With the new case, which is reported in this paper, forty-one examples of
rupture of an aneurysm of the abdominal aorta into some portion of the gastro-
intestinal tract are known to be aA'ailable in the literature. In 71 per cent,
rupture was into the third portion of the duodenum. The condition has been six
times more frequent in men than in women. While the ages were widely dis-
tributed, the occurrence of eight cases between 27 and 32 years-of-age indicates
the importance of this condition in relatWely young patients. The resulting
sj'ndrome combines the features of abdominal aneurysm with those of profuse
hemorrhage into the gastrointestinal tract. Hematemesis, often with abundant
hemorrhage from the rectum, usually marks the onset of the terminal phase.

REFERENCES

1. Rottino, .A.; .Aneurysm of .Abdominal Aorta, With Rupture Into the Duodenum. Case

Report and Review of the Literature, Am. .Heart J. 25: 826, 1943.

2 . Nunncicy. F. P.: .Aneurysm of the Abdominal Aorta, London, 1906, Bailliere, Tindall &

Co.v, 121 pp.

3. Pciias, M. D.; A Rare Cause of Fatal Haematemesis (Rupture of Aneurj’sm of Abdominal

Aorta Into Duodenum), U. S. T. J. Med. 1 : 303, 1941.

4. V'chlinj?, Carl: Perforation der .Aorta in den Digestionstractus, Inaugural Dissertation,

Erlangen, 1878, 40 pp.

5. Wasliburn, R. N., and Wilbur, D. L.: Obstruction of the Duodenum Produced by .Aneurj'sm

of the Abdominal .Aorta, Proc. Staff Meet., Mayo Clin. 11: 673, 1936.

6. Howland, E. S., and Sprofkin, B. E.: Saccular Aneurysm of the Abdominal Aorta. Re-

port of a Case With Terminal .Anuria and Rupture Into the Duodenum, .Am. J. M. Sc.
206: 363. 1943.

7. Hiller, G. I., and Johnson. R. M.: Abdominal Aortic Aneurysm. Rupture Into the Je-

junum Preceded by Occult Blood in the Stool, Am. J. M. Sc. 207: 600, 1944.

S. Morison, J. E.: Rupture of .Aortic .Aneurj'sm Into the Duodenum, Brit. M. J. 2: 244, 1944.
*1. Pratt- Fhoiiiai, H. R.: .Aneurj'sm of the .Abdominal .Aorta With Rupture Into the Duo-
denum. Report of Three Cases, .Am. J. Clin. Path. 14: 405, 1944.

10. Eliason. E. L.. and MeXamee. H. G.: .Abdominal Aneurvsm. .A Report of Twenty-Four

Crises. .Am. J. Surg. 56: 590, 1942.

11. Scott. \ .; .Abdominal .Aneurysms. A Report of Ninetv-six Cases, Am. J. Svph., Conor. &

Ven. Di.v 28: 682, 1944'.

12. Kampmeier. R. H.: .Aneurvsm of the Abdominal .Aorta. .A Studv of 73 Cases, .Am. J. M.

Sc. 192: 97. 1936.

13. Lipshutz, B., and Ciiodoff, R. J.: Diagnosis of Ruptured Abdominal Aortic Aneurvsm.

Report of a Ca«;e, .Arch. Surg. .39: 171, 1939.

14. Man=on, J. S.; Rupture of Aorta Into Duodenum, Brit. M. J. 1: 121, 1937.

AN AURICULAR DIASTOLIC MURMUR WITH HEART BLOCK

IN ELDERLY PATIENTS

David A. Rytand, M.D.

San Francisco, Calif.

, NINE elderly but ambulatory patients with varying degrees of auriculo-

ventricular block, a blowing murmur was heard at the cardiac apex. during
ventricular diastole. Phonocardiograms recorded simultaneously with electro-
cardiograms revealed in each case the vibrations of a murmur, as distinguished
from the abrupt auricular sounds so often observed in complete block, and
showed the relationship of the murmur to auricular activity. At times, the
usual short auricular sounds were also present.

Mitral stenosis did not appear to be present. Calcification of the mitral
annulus fibrosus was found in four cases, but this lesion seems not to alter the
cardiodynamics as does mitral stenosis and fails to produce an auricular (pre-
systolic) murmur when auriculoventricular conduction is normald

The purposes of this paper are to report the observations and to discuss the
mechanisms which might be responsible for the production of the murmur.

case reports

Cases 1 throug;h 4, with calcification of the mitral annulus fibrosus, are the same as those
reported in more detail elsewhere.^ Cases 5 through 9, without calcification, have not been re-
ported before.

Case 1. — A frail woman 74 years of age, with no historj' of rheumatic fever, was found to
have moderate congestive heart failure and complete heart block. At times, the latter was re-
placed by 2:1 block and even sinus rhythm with a P-R interval of 0.19 to 0.21 second, but usually
the block was complete. I.eft bundle branch block was occasionally found, and auricular fibrilla-
tion complicated complete block for two months. The arterial pressure varied ‘around 200/90.
Improvement followed the use of digitalis and diuretics, so that the patient was ambulatory
most of the time. She died at the age of 79 years of cerebral vascular disease; necropsy was not
permitted. During the period in which the observations recorded below were made, signs of
heart failure W'ere virtually absent. The heart did not appear enlarged on physical examination.
X-ray examination, however, revealed slight enlargement; the left auricle was not prominent.
A nearly complete ring of calcification in the region of the mitral annulus fibrosus was seen fluoro-
scopically and recorded on films.

There was a loud, coarse murmur during ventricular systole, best heard along the lower left
sternal border and transmitted to the ape.x, aortic area, and carotid arteries. There was no
thrill. With complete block, the first heart sound varied in intensity and a blowing murmur in
ventricular diastole was heard at the apex. The murmur was enhanced in the left lateral recum-
bent position. Its position in diastole varied, depending upon the time of auricular activity.
The murmur was not heard more than twice in any given diastolic period. When it occurred
early in diastole, it was obviously louder than when it occurred later (Fig. 1).

From tlio Department of Medicine, Stanford University School of Medicine.

■ Receiv^ for publication March 23, 1946,

579

AMERICAN nEART JOURNAL

f . iP

I

rj i'

»l§iil|i§

ric 1 — (’a>,)> 1. SiinuUnnoous records of heart sounds at tho apox and clccirocardiogram. Oom-
ph U' A-V block. Time marking in all figures, 0.0 1 and 0.20 second. The first and second lioart sounds
are <ledgnatfd J and 2; the murmur of ventricular systole. SM; tlio auricular murmur, AAf. Vibra-
tions of (he auricular murmur are smaller both early and late in ventricular diastole (upper strip) than
at inlermtsliaie timr.s (lower strip) and arc not recognizable a.s sucli with Jiormal I’-ji intervals (0.17
secotid in first cycle of lower strip). Small unlabeletl vibrations are artefacts. Upper and lower strips
are eonsecutive.

I hS £

sM-

® ’ I j \

C.ase 1 . .s.'itne as shown in Kig. 1. but during auricular fibrillation. .Small vibrations of
murmur. AM, are relatwl to the second heart souttd.

581

RYTAND : AURICULAR DIASTOLIC MURMUR WITH HEART BLOCK

When 2:1 block was present, the murmur was audible only in the blocked auricular cycle
and not well recorded in the conducted one (P-R interval, 0.24 second; preceding R-R cycle, 1.44
second). In the presence of auricular fibrillation, it was faintly audible and recorded early in
diastole (Fig. 2). It was not heard during the short periods of sinus rhythm, but unfortunately
we were not then aware of the possibility of its existence.

Case 2. — Dyspnea and angina pectoris in a husky man 68 years of age led to the discovery
of calcification in the mitral annulus fibrosus. There was no history of rheumatic fever. After
a period of prolonged conduction time, the P-R interval fell to 0.18 second. Digitalis administra-
tion was followed temporarily by complete block, then 3:2 block; observations noted in the next
paragraph began at this time. Later, even without digitalis, the P-R interval remained fairly
constant at 0.30 second. A year later, auricular fibrillation with slow but irregular ventricular
response appeared and persisted. Congestive heart failure, starting about the same time, finally-
led to the patient’s death two years after the first examination.

The arterial pressure was 135/90. There were no signs of congestive heart failure. The
heart was only slightly enlarged on x-ray examination and the left auricle was not prominent.
There was a loud, rough murmur with ventricular systole, loudest at the base but also heard at
the apex and over the carotid arteries. There was no thrill. With complete block, a rough,
blowing murmur at the apex was audible during ventricular diastole, with behavior similar to
that of the murmur described in Case 1 . The first heart sound varied in intensity (Fig. 3). When
3:2 block was present, the murmur was not heard with the first of the conducted cycles (P-R
interval, 0.24 second), and with such cycles its vibrations were scarcely visible in phonocardio-
grams; under these conditions the preceding R-R cycle length was 1 .38 seconds. With prolonged
conduction time (P-R interval, 0.30 second), the murmur was a presystolic one (Fig. 4).

With congestive failure and auricular fibrillation, the left auricle and the heart became dilated.
The murmur then became confined to early diastole (Fig. 5), was fainter than when associated with
auricular activity, and could not be heard with the patient sitting up.

C.ASE 3. — An obese woman 68 years of age was found in 1939 to have complete heart block,
which persisted until she died of myocardial infarction in 1942. The observations recorded
below were made in 1941, when she was seen because of postural vertigo and when she was some-
what dyspneic but ambulatory. There was no history of rheumatic fever. The arterial pressure
was 270/110, and peripheral arteriosclerosis was marked. There were no physical signs of con-
gestive heart failure, although there was marked cardiac enlargement. Radiologic study re-
vealed calcification of the mitral annulus fibrosus. The left auricle was not unduly prominent.

A thrill at the base accompanied a loud systolic murmur which was transmitted to the apex
and into the carotid arteries. The first heart sound varied in intensity. A soft, blowing murmur
was heard at the apex during ventricular diastole; it behaved quite like the similar murmur de-
scribed in Case 1 (Fig. 6).

. At necropsy, the heart weighed 420 grams. The aortic, pulmonic, and tricuspid valves
were normal. A band of calcification 1 cm. thick and 9 cm. in circumference encircled the mitral
valve in the annulus fibrosus without obstructing the orifice. There was some calcification and
distortion of the mitral leaflets near their base, but their free edges and chordae tendineae were
normal. There was very slight, diffuse endothelial thickening in the left auricle, without striking
enlargement of that chamber. A myocardial infarct was present, and the coronary arteries were
diffusely narrowed. Aortic atherosclerosis Avas marked. Firm masses of calcified fibrous tissue
nearly occluded the proximal portions of the innominate and left carotid arteries.

Case 4. — In 1936, a very small woman 73 years of age developed dA'spnea while at the
Laguna Honda Home. Study of this symptom led to the discovery of complete heart block:
moderate, congestive heart failure was present then, but not later.

Examinations subsequent to 1942 revealed advanced peripheral arteriosclerosis. The
arterial pressure was 220/70. The heart was somewhat enlarged, its rhythm was regular, and the
ventricular rate was 46. There was a rough systolic murmur, faint at the apex, moderate at the
left sternal border, and not reaching the carotid arteries.

5F2

AMERICAN HEART JOURNAL

I'll: ;! - Ca'-o 2 Same as shown In I'Jg. 1. Complete A-V block. Vibration.? of the au-
ricular murmur. AM, arc ftrcatcr early in diastole.

1 ik' ( --Ca'-c 2. Simultaneous records of apical heart soui ds, apex beat, and clectocardiogram. Sinus

rhythm; R-R Interval. 0.30 second.

ric. .0. Ose 2. .?ajne as slionn in Tig. 1 but during auricular fibrillation.

rytand: auricular diastolic murmur with heart block 583

Fig, 6. — Case 3. Same as shown in Fig. 1. Complete A-V bloek. (Ignore the irregular central
tracing.) There is no auricular murmur with the first P wave, P-R interval, 0.20 second, although one
is present with a P-R interval of 0.30 second at the end of another diastole of equal length.

The first heart sound varied in intensity. Systole occasionally contained a loud click. At
the ape.K, a short, blowing murmur was heard at variable times in diastole. It was loud during
early diastole but became faint by mid-diastole. It was never heard late in diastole, but some-
times double auricular sounds were then noted. This murmur was loudest with the patient re-
cumbent or in the left lateral position, but was also present in the upright position. Very re-
cently the murmur sounded rumbling rather than blowing. It was never heard more than once
in anj' one cycle. Phonocardiograms (Figs. 7 and 8) confirmed these signs, showed their relation
to auricular activity, and also revealed a partially split first sound.

Careful radiologic stud)^ in 1942 and 1944 failed to demonstrate calcification of the mitral
annulus fibrosus. However, in October, 1945, that lesion was shown. The left auricle was then
thought to be prominent, although enlargement had not previously been noted. The heart itself
was moderately enlarged as in earlier examinations.

Electrocardiograms always showed complete heart block and left axis deviation.

Case 5. — ^This man was 40 years of age when he first visited Stanford outpatient clinic in
1923 because of pain which was found to be caused by osteoarthritis. There was no history of
rheumatic fever. The heart was normal on physical examination and fluoroscopy. The arterial
pressure was 110/80. An electrocardiogram showed only auricular premature beats.

Repeated examinations were negative as late as 1937, when the arterial pressure was 140/90.
In 1941 the pressure was 160/100; the heart was regular and not enlarged, and there was a loud
systolic murmur over the precordium, loudest along the left sternal border but not reaching the
carotid arteries.

In March, 1942, he visited the cardiac clinic because of pain in the chest which was unrelated
to effort. The heart rate was 53 and the rhythm was regular. There was a loud apical systolic
murmur. During diastole there was also heard at the apex a short, rather low-pitched murmur,
which was quite loud in the left lateral recumbent position. There were no signs of congestion..
The arterial pressure was 140/80. An electrocardiogram showed sinus bradycardia with pro-
longed conduction time (P-R interval, 0.51 second) but no other abnormalities. Careful radiologic
study including fluoroscopy and roentgenkymograms failed to reveal intracardiac calcification.
The heart was not enlarged and the left auricle was not dilated. In 1943 complete heart block
was present ; the ventricular rate was 36 and the first heart sound varied in intensity. Associated
with auricular activity, a blowing but rather low-pitched murmur was heard at the apex in variable
phases of ventridular diastole. The murmur was loudest when it came early in diastole.

In .1944, the patient was requested to return for reexamination. He was then 61 years old
and was working as a, janitor. He appeared to be well and showed no signs of congestive heart
failure. The heart rate was 27 and the rhythm was regular. There was a loud, harsh murmur

I'iir. 5 Sirmiltnitpoub records of the lirnrtsounds at tlioapoA, apox Ijoat, anti oli-ctrocardlo-

(Tram. Complctt* \-V block. TaKon from a continuous tracinp, upper and lower strips were beparatetl
ijj two cjclf"'. Dots indicate xarlalde Inteiisllles of the partially split first Iieart sound. 7n the second
a till third C} ell’s, a 1‘ wa\ e just before the second heart sound is associattsl w ith an auricular sound. A,
In tentrlctdar sj stoic as well as with an auricular niurniur, A'^l. The latter follow.s the second sound
ti) 0 Ofi to 0 <is si-coint At tlmrsi. as in the s(*cond cjcle, xibratlons followlnp the auricular sound durlnp
t CTiSrlctilar sj stole resentble those of a murmur.

rytand: auricular diastolic murmur with heart block

585

at the apex and especially at the left sternal border during ventricular systole. A third heart
sound was audible at the apex and was followed immediately by a blowing murmur. Auricular
sounds were barely audible late in diastole (Fig. 9). An electrocardiogram showed 2:1 A-V block.

Case 6 . — A man 59 years of age had visited the cardiac clinic for two years because of angina
pectoris and dyspnea on effort. He had a history of six attacks of gonococcal urethritis with
arthritis, three of them under observation. There was no history of rheumatic fever.

Fig. 9. Case .5. Simultaneous records of heart sounds at the apex, apex beat, and electrocardio-

gram. 2:1 A-V block. Upper strip, sensitized paper moving at 75 mm. per second; lower strip, at
25 mm ’ per second The first and second components of auricular sounds vith the conducted P wave
are designated. and is the murmur initiated by the third heart sound, The latter coin-

cides with the thrust x of the apex beat. A” with the oppositely directed thrust y. With the second
and sixth P waves in the lower strip, sound \ibrations appear less like those of murmur than like those
of double sounds; the second components of these coincide with additional waves in the apex beat.

When the patient was first seen, the heart rate was 60 and the rhythm was regular. No
murmurs were noted in the clinic record. The arterial pressure was 180/105. An electrocardio-
gram showed sinus rhythm ivith P-R intervals of 0.32 second. When the heart sounds were
recorded. (Fig. 10) in 1942, there was transient complete heart block but no s(gns of congestive
failure. A faint, blowing apical murmur was noted early in diastole. Radiologic study show'ed
the heart and left auricle to be normal in size. Intracardiac calcification was specifically looked
for but was not found.

586

AMERICAN HEART JOURXAL

At the present time he is in the San Francisco Hospital with moderate congestive failure and
iiiconipleie heart block. .\ blowing apical murmur was heard at varying times, especially in
early diastole; it was present with the patient in an upright position as well as in a supine; no
other signs of mitral stenosis were found.

’ I I I . |M

I '

Rig. 10. — Case f>. KlmuUaneous ri'cords of the heart sounds at the aptyc, jugular pulse, and electro-
cardiogram. Complete .V-V block. Upper and lower strips arc consecutive. The auricular murmur.
••1,1/, was audible when tlio P wave began 0.10 to 0 18 second after the start of the second heart sound.
It was probably inaudible when that Interval was 0.22 to 0.28 second. No systolic murmur is recorded.

Casi: 7. — ,\ healthv woman 70 years of age consulted a surgeon in 1943 because of ulcers
which complicated varicose \eins. .\ murmur was heard in the course of a general e.xamination.
There was no history of iheumatic fever.

Fig. 11, — Case 7, Slmultaneou.s records of licart sounds at the ape\ and eicctrocardiograni. .Sinus
rhythm, P-H interval, 0.20 second. The u.sual auricular murmur, AM, is occasionally replactsl by vi-
brations of a -snunfl. S, There is al<o an evtr.a sound, x, during ventricular sy.stolc.

RYTAND : AURICULAR DIASTOLIC MURMUR WITH HEART BLOCK

587

The heart was not enlarged, its rate was 76 , and its rhythm was regular. There was a
presystolic blowing apical murmur, as well as a loud, rough systolic murmur over the entire pre-
cordium (Fig. 11). There were neither signs nor symptoms of congestive failure. Peripheral
arteriosclerosis was moderate. Arterial pressure was 200/100. The electrocardiogram re-
vealed only prolonged conduction time (P-R 0.26 second). No calcification could be found within
the heart on fluoroscopy or in x-ray films. The heart size was at the upper limits of normal;
there was no auricular dilatation.

Case 8. — A man 53 years of age requested a cardiac examination. He had had chorea re-
peatedly over three years as a child, and was first told of a murmur when 21 years of age. More
recently, hypertension and weakness appeared, and a month before he was seen here there had
been an episode resembling pulmonary infarction.

The heart was of normal size, the rhythm was regular, and the rate was 60. There was a
blowing presystolic murmur (Fig. 12) and a soft systolic murmur at the apex. The first sound
at the apex was split and was not loud. Earfj'- diastole was clear. Arterial pressure was 160/100
but fell to 140/85 after a few days in bed. There were no signs or symptoms of congestive failure,
and peripheral arteriosclerosis was slight. An electrocardiogram showed prolonged conduction
time (P-R interval, 0.32 second) and abnormal T waves, without axis deviation. Careful
radiologic study revealed no general cardiac or left auricular enlargement, and no intracardiac
calcification.

Fig. '12. — Case 8. Simultaneous records of the heart sounds at the apex, apex beat, and electro-
cardiogram. Sinus rhythm, P-R interval 0.32 second. The auricular murmur, AIM, often starts
abruptly. The first heart sound is usually split, 1, 1'. The sj'stolic murmur, SM, is inconspicuous.

Case 9. — ^A woman 60 years of age gave a history of some sort of rheumatism in childhood.
Starting at the age of 24 years, she became progressively more crippled by rheumatoid arthritis.
About this time she becan to have attacks of paroxysmal tachycardia which became temporarily
worse in 1944 when she entered Lane Hospital.

Examination showed extensive rheumatoid arthritis and emaciation but no congestive
failure. The arterial pressure was 190/110. There was relatively slight peripheral arteriosclero-
sis. The heart was moderately enlarged. Its rhythm was disturbed by auricular and ven-
tricular premature beats and bj' paroxysms of auricular tachycardia. The first heart sound was
widely split; there was a loud, blowing murmur between its two elements, best heard at the apex.
Diastole was clear; the few presystolic vibrations seen in the sound records (Fig. 13) are probably
not a murmur. Electrocardiograms showed P-R intervals of 0.16 to 0.18 second and a wide
QRS complex with deep, broad S waves in Lead 1. Simultaneous records of the electrocardio-
gram, heart sounds, and carotid pulse confirmed the presence of right bundle branch block.
Radiologic study revealed a moderately enlarged heart but no auricular dilatation or intracardiac
calcification.

5

AMERICAN HEART JOURXAE

!>urinc ctn aiuirk of auricular tachycardia, the electrocardiogram showed Wenckebach’s
Simiiltancou? records of the heart sounds at the apex (Fig. 13) revealed vibrations of
a murnnir in the cycles having long P-R intervals and especially in with those with blocked P
Tile murmur was not recognired on auscultation.

\ vdir later an exec'^ive dose of digitalis was followed by an arrhythmia in which the P
i.aM- and R.S-T coinplc.xcs were occasionally dissociated, each having a normal rate. When
P v.av<- appt-ared shortly after the T wave, there was usually a longer-ensuing pause. In

lower ctclc', an early short, blowing diastolic murmur was occasionally heard at the apex.

1 , . w.is confirmed at the San Francisco Hospital, but further phonocardiograms could not be
o'.r.'.titd Xo signs of mitral .stenosis were found. The heart was enlarged, and the radiologists
' I the left auricle was overly d'latcd.

Fi;t. i;t. — Case 0. Heart sounds at tlic apex and electrocardiogram. Above, sinus rliytlun, P-K
Interval. «.ts serond. The flrsl heart sound is widely split, 1, 1', with an unlaheleti murmur betwoen
the t«o coni|)onents and a feiv pre.systoiic vibrations (not thought to constitute a murmur) before tlio
fir.st eoini>oneti!, Hclow, auricular tacliycardla with 'Wenckebacli periods. Vibrations of ati auricular
murmur. M. are vlsllile with lengtbcning I’-R Intervals and especially in cycles with complete block.

OBSERVATIONS

A blowing murmur restricted to tlie apex was clearly heard during ventricular
diastole ju each of the cases described. Records of the heart sounds in all nine
case.s showed the vibrations of a murmur, as distinguished from the usual abrupt
auricular sounds which occur with heart block, although the latter were occa-
sionally found also. The murmur was louder with the patient in the left lateral
recumbent or supine position but could be heard in the upright position except
when auricular fibrillation was pre.senl. With complete heart block its temporal
position varied from cycle to cycle, depending upon the time of auricular activity.

RYTAND : AURICULAR DIASTOLIC MURMUR WITH HEART BLOCK 589

It could then usually be heard twice in each cycle and was always louder when it
appeared fairly early in diastole. There was no opening snap of mitral stenosis
in any of the patients, and the murmur was never constantly related to the second
heart sound except as noted later in the paper.

The following measurements were made on simultaneous records of the heart
sounds and an electrocardiographic lead, avoiding parallax; in some cases cardio-
vascular pulsations were also recorded. It is recognized that these data are not
as accurate as could be desired because of such difficulties as locating the earliest
vibrations of the murmur. Nevertheless, some of the findings seem significant.

Interval from P Wave to Murmur. — The interval between the onset of the P
wave of the electrocardiogram and the onset of the murmur averaged 0.15 to
0.16, 0.16, 0.23, 0.18, 0.14 to 0.16, 0.17, 0.16, and 0.18 second in Cases 1 through 8,
respectively.

Interval From Seco7id Heart Sound to Murmur. — Except under special condi-
tions, there was no murmur related by a definite time interval to the second heart
sound. In Case 1 a murmur was often recorded with onset about 0.12 second
after the second sound whenever a P wave began just before that sound (Fig. 1).
The amplitude of these vibrations was less than when the murmur appeared
later in diastole. In Case 4, the second heart sound often preceded a murmur by
0.06 to 0.08 second whenever the P wave fell comparatively late in ventricular
systole (Fig. 8).

With auricular fibrillation in Cases 1 and 2, a faint apical murmur was found
in early diastole (Figs. 2 and 5). It started about 0,19 second after the second
heart sound in Case 1, 0,12 second or less in Case 2.

Auricular Sounds. — In some of the patients phonocardiograms at times
revealed abrupt auricular sounds, as distinguished from murmurs.

In Case 1, vibrations incorporated within the auricular murmur resembled
those of a sound when the murmur began, roughly, 0.3 to 0.6 second after the
second heart sound. These vibrations occurred about 0.21 second after the start
of the P wave.

In Case 4, the murmur was only heard very early in ventricular diastole.
Phonocardiograms (Fig. 7) show that its vibrations became small rather suddenly,
in different cycles, whenever the P wave began later than about 0.5 second after
the last second heart sound. With P waves later than that, there were a few small,
slow vibrations starting 0.20 second after the onset of the P wave. These did not
differ appreciably whether their associated P wave began 0.6 or 1.3 second after
the last second heart sound. They were sometimes identified on auscultation as
faint, double auricular sounds but were usually inaudible. In this patient, in
whom tlie murmur of ventricular systole was short and faint at the apex, a loud
clicking auricular sound was occasionally heard and recorded before the second
heart sound. Late in ventricular systole such sounds started 0.10 second after
the P wave, while earlier in systole the interval was about 0.14 second. The
recorded appearance of the sound varied (Fig. 8) and occasionally even resembled
that of a murmur.

590

AMERICAN- HEART JOURNAL

In Ca?e 5, with 2:1 block, auricular sounds were associated with both blocked
and conducted (P-R interwal, 0.45 second) P waves. With the latter, double
auricular sounds (faintly audible but not separated on auscultation) were recorded.
The finst component occurred 0.14 second and the second component 0.28 second
after the onset of the P wave. The blocked P wave, which started 0.06 second
after the .‘second heart sound, was followed 0.16 second after its onset by a loud
third heart sound which Avas noted clinically and initiated the auricular murmur.
On the other hand, records occasionally showed vibrations Avhich looked like a
murmur with the conducted cycle. Finally, the usual murmur following the
third sound was sometimes absent. In this event there was usually a fourth
sound, 0.16 second after the third and associated with a downward deflection
of the ape.x beat curve (Fig. 9). In this patient, records made during complete
block showed only a murmur, starting 0.14 to 0.16 second after the P Avave.

In Case 7, especiallj' Avith the patient in the left lateral recumbent position,
the murmur AA'as sometimes initiated or replaced by a recorded vibration Avhich
had the appearance of a sound (Fig. 11). A mid-systolic click aa'Us also noted.

Apex Beat. — In Case 5, a sharp upAA^ard deflection of the ape.\ beat curve
accompanied the third sound, Avhich folloAA'ed the onset of the blocked P AA'ave
by 0.16 second and Avhich AA'as at once folloAA'ed by the auricular murmur (see
also preceding section). In the same patient, the second component of the auric-
ular sound Avith conducted P AA-ave AA'as associated in the ape.x beat Avith a sharp
doAA'nAvard deflection 0.28 second after the onset of the P AA'ave, folloAA'ed at once
by a sloAv rise (Fig. 9).

A similar sIoav, small rise in the apex beat curA'e began 0.16 to 0.24 second
after the onset of the P AA'ave in Case 2 and 0.16 second in Cases 3 and 8. The
significance of this rise is not clear, but it is not thought to represent auricular
systole.

In Case 4 (Fig. 8) a larger upAA'ard moA'ement of the recorded apex beat
began 0.14 second and reached its peak 0.22 second after the onset of the P Avave.
It did not occur AA'ith P AA’aves during ventricular systole and its appearance and
timing did not vary Avith the location in ventricular diastole, a finding AA'hich may
be related to the folloAving obserA'ation.

Jugular a Wave. — The behaA'ior of the jugular a AvaA'C AA'as especially note-
Avorthy in Case 4. When the a AA'aA'e occurred late in A'entricular diastole Avithout
an audible murmur, its amplitude AA'as no greater than that of an a AA'ave asso-
ciated Avith a murmur early in diastole. The same records shoAv markedly in-
creased amplitude of a AvaA'es during A'entricular cystole, as expected (Fig. 7).
Judging by this obser\'ation, A'entricular filling eA'en for 1.3 seconds after the
last second heart sound (and further aided by tAA'o interA'ening auricular systoles)
does not impede outfloAv from an auricular contraction occurring late in A'entricular
diastole.

In Cases 2 and 4, the murmur began at or after the peak of the a Avave, a
point Avhich aams also associated Avith the first component of the double auricular
s<iund in Case 5.

RYTAND : AURICULAR DIASTOLIC MURMUR WITH HEART BLOCK 591

The jugular a wave began 0.08, 0.10, 0.10, and 0.09 second after the onset
of the P wave in Cases 2, 4, 5, and 6, respectively. Since these findings are
in the normal range, they indicate no delay in right-sided auricular systole.

DISCUSSION

Mitral Stenosis . — ^An apical murmur related to auricular activity is at once
suggestive of mitral stenosis, but that lesion did not appear to be present. Cal-
cification of the mitral annulus 'fibrosus, such as found in Cases 1 through 4,
might be expected to obstruct flow through that orifice but actually does so only
rarely; in five other patients with calcification but with P-R intervals of 0.14
to 0.18 second this murmur could not be heard or recorded.^

No patient had the other physical signs of mitral stenosis; namely, loud or
split pulmonic second sound, loud first heart sourfd (except when accentuated in
cycles with short P-.R intervals), opening snap, or early diastolic murmur con-
stantly related to the second sound (in the absence of auricular fibrillation).
Right axis deviation was never present, nor was the P wave abnormally large.
The left auricle was not often prominent, except with general cardiac enlarge-
ment or auricular fibrillation. Although the auricular murmur, was enhanced
in the left lateral recumbent position, it was usually blowing in quality, quite
unlike the rumble of rheumatic mitral stenosis; in Case 2 it was rather rough,
and in Case 4 became rumbling after several years.

Aortic regurgitation was not present, so the Austin Flint murmur need not be
considered. An auriculo-systoUc murmur which has been heard at the tricuspid
area during convalescence from myocardial infarction- is likewise unrelated to the
present discussion.

A murmur suggestive of mitral stenosis has been found in patients without
that lesion but with anemia^’^ or congestive heart failure®’® and is usually attrib-
uted to stenosis relative to dilated cardiac chambers. While congestive failure
was sometimes present, it was never more than mild when the foregoing observa-
tions were made in these ambulatory patients, of whom none was anemic. Heart
block itself produces cardiac dilatation but has never been thought to cause a
murmur. Stenosis of the mitral orifice relative to such distention should give a
murmur louder in later diastole, whereas the opposite was true.

One of the main reasons for rejecting mitral stenosis, actual or relative, as
the cause of the murmur is the latter’s delayed onset after the P wave. Probably
because of the difficulties in locating accurately the onset of a murmur in records
of the heart sounds, there are but few data to indicate the temporal relationships
of the presystolic murmur in rheumatic mitral stenosis. Calculations based on
the observations of Lewis' and BramwelP suggest that such a murmur starts
0.03 to 0.15 second after the beginning of the P wave, with which a few records
in this laboratory agree. In the present patients the murmur began 0.14 to
0.23 second after the P wave. Their jugular a waves revealed no delay in the
onset of right auricular contraction, and there is no reason to believe that systole
of the left auricle did not coincide \yith that of the right. Furthermore, it was

AMEKICAX HEART JOURNAL

5*>2

.>o.sibk- to find c>-cles with normal P-R intervals in the patients with complete
heart i>}ock. At such limes vibrations of a murmur were not Ausible in the phono-
cardiop^rams (Figs. I and 6).

'IVmporarily ignoring its presence early in diastole with auricular fibrilla-
o ai. the murmur appears to be an event which follows auricular contraction.
'I'he t \!dence gi\-en seems to indicate that it is neither caused by obstruction to
fir. VI rir.r a)incidenl with auricular s 3 'stole.

Milral hssufTideJicy . — It is conceivable that the apical murmur which follows
.ii'ei auricular sj'stole during ventricular diastole is the result of regurgitation
(,f l.ior.d back into the auricle, with mitral insufficiency.

If this were the ca.se. a murmur might also be e.vpected to occur at the close
(.1 I he period of early diastolic rapid filling. This did occur faintly in Cases 1
.md 2 during auricular fibrillation, but only then. Regurgitation perhaps should
.iF') increase, presumabh' with a louder murmur, when the ventricles are more
full 1-ue in diastole. Observations showed the opposite.

•Mitral insufficiency as a cause of the murmur would be supported by its
demonstration during ventricular systole. With the slow rate of heart block and
with arterial hypertension, circulator}' conditions were optimal for regurgitation
of blood if mitral insufficiency were actually present.® A sj'stolic murmur was
frequently heard at the ape.K, and in a general wa}' its intensity was paralleled by
that of the auricular diastolic murmur. However, it was usually fainter at the
apex th.'in along the left sternal border, was once confined to the interval between
the widely split components of the first heart sound, and was not conspicuous
in e\'ery case. It might have been produced by aortic dilatation with arterios-
clerosis.

It is generall}' held, though perhaps incorrectly, that mitral regurgitation
may be present without radiologic evidence of left auricular dilatation or abnormal
pulsation of that chamber in roentgenkymograms. At any rate, the left auricle
was not prominent in an)' of the patients during the period in which most of the
observations were made. It did, however, enlarge somewhat later on in Cases 2,
9, and perhaps 4. This might have been the result of auricular fibrillation and
progressive congestive failure. Study of the roentgenlcymograms in Cases 1,
2, 4, 5, and 6 showed none of the findings thought to be typical of mitral regurgita-
tion.'®

In brief, regurgitation through the mitral leaflets at the close of auricular
SNstole may be a simple explanation for the murmur, but there is little evidence to
sub.stantiate its occurrence. . The frequent association of the murmur with auric-
ular sounds and its occasional replacement by them are adequate reasons for
consideration of other possible mechanisms.

Relaliov lo Heart Block . — The murmur occurred only in patients with heart
block. Auricular activity during that arrhythmia ordinaril}' results in abrupt
sounds, not mtirmur.s. At times, phonoairdiograms of this event have revealed
prolonged vibrations” which do not appear to have been clinicallj' interpreted as
murmurs.

RYTAND : AURICULAR DIASTOLIC MURMUR WITH HEART BLOCK 593

Wolferth and Margolies^^ and Stead and KunkeP-'^ reported two cases of
heart block, each with an audible murmur similar to that now being discussed.
The causes of block were not altogether clear. There were no other signs of
mitral stenosis, and the patients were aged 49 and 57 years. The murmur started
0.14 to 0.16 second after the onset of the P wave. Apparently the murmur was
not present in Case 1 of Wolferth and Margolies’ series during periods of sinus
rhythm with normal P-R intervals. A presystolic murmur was heard and re-
corded in the case of Stead and Kunkel with the P-R interval as short as 0.20
second (during 2 :1 block) and- was noted during sinus rhythm with which the
P-R interval was never found to be less than 0,22 second. These two cases and
the nine reported here seem to be the only recorded instances of audible auricular
murmurs in heart block (without obvious mitral stenosis). Such a murmur will
surely be found more often in elderly patients with defective auriculos^entricular
conduction, once the possibility of its occurrence is appreciated.

Limitation of the murmur to patients with heart block must be the result
simply of delayed ventricular contraction, permitting an adequate interval of
time to elapse after the conclusion of auricular systole; the conditions productive
of the sounds or murmurs which may be heard in this interval would otherwise
be prevented.

Heart Sounds During Ventricular Filling . — Since the murmur began 0.14
to 0.23 second after the start of the P wave, or about 0.12 to 0.19 second after
the second sound in the presence of auricular fibrillation, it becomes pertinent to
inquire into what is known of cardiodynamics and sounds during those periods.

Early in diastole, ventricular filling commences abruptly at the time indi-
cated by the position of the opening snap of mitral stenosis, 0.07 to 0.13 second
after the second heart sound. This phase of rapid filling comes to an end 0.12
to 0.20 second after the second sound. Here a normal third heart sound or an
early diastolic gallop may be present‘d and this is the range of time in which the
murmur began in Cases 1 and 2 in the presence of auricular fibrillation.

In both laboratory animals and man,’® auricular systole appears to begin
about 0.03 to 0.04 second, and the jugular a wave about 0.08 to 0.10 second,
after the start of the P wave. In at least four of the present patients jugular a
waves indicated no delay in the onset of mechanical systole of the right auricle.
The duration of increased intra-auricular pressure may be 0.13 to 0.15 second.’’'’’®
Therefore, the phase in which ventricular filling is accelerated by auricular systole
is at an end some 0.16 to 0.19 second from the start of the P wave. This, roughly,
is in the time range of the onset of the murmur now under discussion. It is also
near the time at which another sound may be recorded; while a presystolic gallop
is often found 0.08 to 0.14 second after the beginning of the P wave, this interval
lengthens in ambulatory patients with milder, congestive failure to 0.12 to
0.17 second.’®

Some of the auricular sounds found in heart block follow the P wave by
an even greater interval. Omitting a preliminary sound recorded only from the
auricular wall or through the esophagus, two groups of workers”’^® place the first

AMERICAN HEART JOURNAL

5<n

of audible auricular sounds at 0.06 to 0.08 or 0.12 second and the
..n-nnt! roniponeni at 0.17 lo 0.24 or 0.20 to 0.24 second from the start of the P
(Hr findings are in better agreement tvith Wolferth and Margohes.i^
ni,., -rx. int. rvals of 0.08 to 0.14 and 0.24 to 0.30 second, respectively, for the
■ w r.-mp.-iu ni'- We also agree with the latter observers that it is only the
• .• .r.iuponent which is recorded during ventricular systole.

\- part of the variations and discrepancies in the foregoing data

tn>\ ri -ult from din'erences in age, degree of heart failure, presence of valvular
o! .'Irr le-ions. etc., in the patients studied; it might be more helpful if future
< !t- on heart .‘^ounds considered some of these factors. Clarification of the
;,!■ -fut uncertainties as to the causes of diastolic sounds would obviously be

..ir.itix (it•^irahle.

Ha-ed in part on Dean’s-^ experiment, Lewis and Dock--’®'’ suggested that
till’ thiid heart sound and gallop sounds may occur at the end of rapid-filling
[4i.is<-s if the auriculoventricular valve leaflets are then closed or drawn taut.
\i.i all workers agree with this view.*® Dean,-* using the excised heart of the
I a' . found that the mitral cusps swing up and are momentarily approximated
at about 0.15 second after the start of mechanical auricular systole. The cusps
-f'parate again 0.12 second later. These times come 0.18 and 0.30 second after
I he onset of the P wave, and the first is compatible with the start of the murmur;
for comparison with Dean’s time of valvular separation, the final vibrations of
the murmur occurred about 0.31 to 0.37 second after the onset of the P wave in
Cases 1 through 6. There is, of course, an obvious risk in comparing events in
tweised cat hearts and abnormal human hearts.

The data presented in this section are consistent wdth the view that the
murmur in these elderly patients starts near the end of phases of accelerated
ventricular filling, at times when short sounds may be heard in other subjects.
Such sounds, in fact, occurred in the present patients occasionally, either replacing
the murmur or associated with it. The temporal relationships of the murmur are
similar to those of a period during which experimental studies have demonstrated
the approximation of mitral leaflets following auricular systole. Approximation
was not found after the early diastolic phase of rapid filling,®* nor did the murmur
occur then except twice; on both occasions auricular fibrillation was present and
the murmur was much fainter.

It seems very likelj' that the murmur is produced by some mechanism which
does not interfere with the movements of the valve leaflets during periods of rapid
flow but which modific.s their presumably more delicate aftermovements.

of ihc Volvc Leaflets . — ^This sort of mechanism might have an anatomic
f.vplanation in the. increased thickness and rigidity of valve leaflets known to
occur with advancing years, especially on the left side of the heart.®®-®® There
seems to be no direct information regarding the effect of aging on the mobility
of leaflets, but some indirect data may have a bearing.

Wolferth and Margolies’® found, in txvo young patients with heart block,
two ?one.s of intensification of the first heart sound; the first was with P-R in-

595

RYTAND : AURICULAR DIASTOLIC MURMUR WITH HEART BLOCK

tervals of less than 0.14 to 0.20 second, the second with P-R intervals greater
than 0.32 second. In three older patients the second zone was not present.
These findings have been confirmed by unpublished observations in this labora-
tory. Expressing the results differently, the first heart sound is relatively faint
in children when the P-R interval is between 0.14 to 0.20 and 0.32 second, the
time of the murmur in our patients and that of approximated mitral leaflets in
Dean’s^^ experiment. It is faint in elderly patients at all times after P-R in-
tervals of 0.14 to 0.20 second.

The explanation of the variable intensity of the first heart sound in block
is not entirely clear, but the hypothesis that accentuation takes place whenever
“systole occurs at an instant when inflow from the auricle is pushing the valves
toward the ape.x and separating the leaflets as much as possible”22 is attractive
and appeals to others. The corollary is a faint first heart sound whenever the
lea^ets are approximated at the onset of ventricular cystole. According to this
view, the mitral leaflets of children swing apart again some 0.32 second after
the P wave, while those of older subjects do not.

The forces concerned with the play of the cardiac valves during ventricular
diastole are not definitely known”® but maj^ involve eddy currents or “the lateral
inrush into the wake of the breaking jet just beyond the ostium. An inrolling
type of motion of pliable young leaflets with the force of lateral inrush is thought
to close the valve without regurgitation; rigid old leaflets, swinging like a door
on hinges, may permit regurgitation.^’ Furthermore, the leaflets of the elderly
are said to be “less nicely approximated than in youth, again suggesting regurgi-
tation as the cause of the murmur.

On the other hand, these forces may be sufficient to narrow the mitral orifice
while blood is flowing through in a fonvard direction,^®’-® apparently even with
thin normal leaflets. If this is so, it is conceivable that the murmur is produced
by the more prolonged apposition of thick, rigid cusps under similar conditions,
perhaps with vibration of the leaflets.

Since valvular aging appears to begin in the second or third decades, this
may be at least a partial explanation for the decreasing frequency of the normal
third heart sound with age. Leaflets becoming less pliable might fail at normal
pressures to behave in the manner thought to produce the third sound^- but could
again respond to the increased intra-auricular pressure of heart failure with a
gallop sound.

The Murmur in Relation to Phase of Ventricular Diastole . — In general,
records of the heart sounds revealed that the greatest amplitude of the murmur’s
vibrations was found when the murmur began near the end of the early diastolic
rapid-filling phase (Figs. 1,3,6, 7, 8, and 10). The vibrations were usually smaller
after this period, except for a few of large amplitude, as if a sound were bracketed
by the murmur. They were certainly smaller before this period. This fact
may be less significant because the associated P wave often started in or near the
end of ventricular systole.

AMERICAN HEART JOURNAL

5'%

Uthf-r (ibs-erver? ' have also noted the diminishing intensity of auricular
iinrnnir- in heart block as auricular activity comes later in ventricular diastole.
Then explanation is that during diastole the filling ventricle becomes

iLh 'O receive blood with later or successive auricular contractions. This
, -o i.bMoiis that it came as a surprise to find both old-® and new^® experi-
• fill h "Uggest that this need not be so.

1 , ( IN- 4 the behavior of the jugular a wave failed to reveal right ventricular
, . \ 'n receive blood late in diastole. Its amplitude and duration were no

> i > Iren it occurred more than 0.5 second after the second sound, without
',!'!(■ murmur, than when it occurred less than 0.5 second after the second
. ■ (i Slid \uth a murmur (Fig. 7). With the closed valve of ventricular systole,
. . w ive wah tall, as expected. In fact, the tracing seems to show broader and
i- ps.iki'd a waves early in diastole, especially with the earliest and greatest
!!'.!>' miTN If this is significant at all, it is in the direction of supporting the con-
, ( P <if j^reater resistance to auricular systolic ejection when this comes with the
( I i\ (.ipid-filling phase.’®

In other patients the murmur occurred at any time in diastole, starting as
I , ( .i.s 0.8, 0.9, and 1.1 seconds following the last second heart sound in Cases 1,
5. and 5, even though the auricles had contracted once before in those cycles.
C!ti.->er inspection of Fig. 14 for Case 1 of Wolferth and Margolies’ series’^ lends
further support to the conception that the murmur’s amplitude is not so much
(h'crea'ied in late diastole as it is increased when approaching the zone of the
third heart sound. The latter was pointed out in their legend.

When the P-R interval of the final P wave in a ventricular diastole tvas

t) 20 second or less, no vibrations of a murmur were recognizable. With P-R
intervals just a few hundredths of a second longer, vibrations were readily appar-
ent (Figs. 1 and 6). Such a short difference of time cannot well explain the
ab'Cnce of the murmur by further ventricular filling in that interval but must be
taken as confirmation of a relatively late onset of the murmur after the P wave.
I fns is anaiagous to the absence of a murmur in elderly patients with normal
conduction times.

Incidentally, the first heart sound was accentuated in Cases 1, 3, 4, and 5
with short P-R intervals, but not when the P-R interval xvas long enough, 0.20
second or more, to permit recognition of a murmur’s vibrations. This probablj'^
means the mitral leaflets were no longer widely separated by auricular systole
when the murmur was produced, in further agreement with its delayed onset.

The early, rapid-filling phase failed to provoke any but a faint murmur
which occurred twice and only with auricular fibrillation. Even auricular systole
w.is not alw.'iys followed by the murmur, especially after a long diastole. Appar-
ently the two events are more powerful when in conjunction, in which connection
it is interesting that Cossio-" found a third sound with heart block when the P
w.u'c fell immediately after the T wave of the preceding cycle in patients who
nthcrwiic had neither auricular sounds nor third heart sounds.

Ax an alternative to mitral regurgitation, the following hypothesis is proposed.
.After auricular systole, nonnal mitral leaflets are floated nearly together. In

rytand: auricular diastolic murmur with heart block 597

the aged, they remain longer and more fixed in that position because of their
increased rigidity. The murmur occurs then with continuing forward flow
through the relatively narrow orifice. It is loudest in the part of early diastole
which follows the phase of rapid filling because the valvular play after this event
reinforces the valvular play after auricular systole and because the blood flow
is still great. When the murmur disappears or is replaced by the usual short
auricular sounds in late diastole, it is because the flow has become slow. This
is more the result of moving awaj'^ from the early phase of rapid filling than of
ventricular inability to receive blood. The lesion is not adequate to hamper
flow during the rapid ejection phases themselves.

SUMMARY AND CONCLUSIONS

Observations are reported on a blowing apical murmur related to auricular
activity in nine elderly patients with heart block. At times the murmur was
associated with, or replaced by, short auricular sounds.

There was no convicing evidence of rheumatic mitral stenosis. Calcifica-
tion of the mitral annulus fibrosus was demonstrated in four cases. Other pati-
ents with this lesion but without conduction defects do not have such a murmur..

The onset of the murmur seemed to occur just after the end of auricular
systole. In the presence of auricular fibrillation, it began near the end of the
rapid-filling phase of early diastole. These are the times at which gallop sounds
may be present in other patients.

In the absence of auricular fibrillation, there was no murmur in relation to
the second heart sound unless auricular activity happened to take place at
that time.

The murmur was loudest when auricular activity more or less coincided with
the end of the early rapid-filling phase. Both earlier and later in diastole, the
murmur was fainter.

An explanation other than inability of the filled ventricle to receive blood
late in diastole is offered to account for the diminished intensity of the murmur
at that period.

Mechanisms which might be responsible for the production of the murmur
are discussed in relation to current conceptions of cardiodynamics and heart
sounds during ventricular diastole.

Reasons are given for believing that the murmur may be caused by modifica-
tions of the movements of the mitral valve leaflets at the end of periods of accel-
erated ventricular filling, especially after auricular systole.

The lesion responsible for such a mechanism may be the result of aging of
the leaflets, without interference to flow during rapid ejection phases.

Tt is further suggested that aging of the leaflets could account for the dis-
appearance of the normal third heart sound and its return as a gallop during heart
failure.

This is another murmur which ma3'^ be heard at the cardiac apex during
diastole in the absence of mitral stenosis.

59B

AMERICAN HEART JOURNAL

REFERENCES

] Rvtand D. A., and Lipsitch, L. S.: Clinical Aspects of Calcification of the Mitral Annulus
' Fihro>us, Arch. Int. Med. In press. ^ ,

5 U’olfcrth, C. C., U'ood, F. C., and Margolies, A.: An Aunculosystolic Murmur m the

'■ IVicuspid .“irea” During Convalescence From Acute Coronary Occlusion, Am. J. Med.
Sc. 186: 496, 1933.

; Gold>tein, 13., and Boas, E. P.; Functional Diastolic Murmurs and Cardiac Enlargement in
Severe .Anemia, Arch. Int. Med. 39; 226, 1927.

; Wincor, T., and Burch, G. E.: The Electrocardiogram and Cardiac State in .Active Sickle-
Cfli .Aricmia, .Am. Heart. J. 29: 685, 1945.

' \\'<>in-t'--in 11'., and Lev, M.; Apical Diastolic Murmurs Without Mitral Stenosis, Am.

Heart J. 23: 809, 1942.

6 Robinow, M., and Harper, H. T., Jr.: Functional Mitral Stenosis, Ann. Int. Med. 17 : 823,

1942.

7. Lewis, T.; The 'Fime Relations of Heart Sounds and Murmurs, With Special Reference
to the .Acoustic Signs in Mitral Stenosis, Heart 4: 241, 1912.

S Bramwell, C.: Sounds and Murmurs Produced by Auricular Systole, Quart. J. Med. 4;
139, 1935.

0 Wiggers, C. J., and Feil, H.: The Cardiodvnamics of Mitral Insufficiency, Heart 9: 149,
' 1922.

10. Hirsch, I. S., and Gubner, R.; .Application of Roentgenkymography to the Study of Normal
and .Abnormal Cardiac Physiology, Am. He.art J. 12: 413, 1936.

1 !. On'a.s. 0., and Braun-hlenendez, E.; The Heart-Sounds in Normal and Pathological Con-
ditions, London, 1939, Oxford University' Press.

12. Wolferth, C. C., and Margolies, A.: The Influence of Auricular Contraction on the First

Heart Sound and the Radial Pulse, Arch. Int. Med. 46: 1048, 1930.

13. Stead, E. A., Jr., and Kunkel, P.: Factors Influencing the Auricular Murmur and the

Intensity of the First Heart Sound, Am. Heart J. 18 : 261, 1939.

14. Stead, E. .A., Jr.: Personal communication.

15. Wolferth, C. C., and Margolies, A.: Heart Sounds. In Stroud, W. D. (editor): The

Diagnosis and Treatment of Cardiovascular Disease, ed. 3, Philadelphia, 1945, F. A.
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16. Taquini, A. C.: Exploracion del Corazon Por Via Esofagica, Buenos Aires, 1936, El Aleneo,

p. 32.

17. Wiggers, C. J.: The Physiology of the Mammalian Auricle. I. The Auricular Myogram

and .Auricular Sj'stoie, Am. J. Phy’siol. 40: 218, 1916.

18. Jochim, K.: The Contribution of the Auricles to Ventricular Filling in Complete Heart

Block, Am. J. Phy'siol. 122: 639, 1938.

19. Lewis, J. K.: Nature and Significance of Heart Sounds and of Apex Impulses in Bundle

Branch Block, Arch. Int. Med. 53; 741, 1934.

20. Cossio, P., Berconsky, I., and Trimani, A.: Genesis di los Ruidos Auriculares Diastolicos

cn el Bloqueo -Auriculoventricular Complete. Rev. argent, de cardiol. 9: 238, 1942.

21. Dean, .A. L., Jr.: The Movements of the Mitral Cusps in Relation to the Cardie Cy'cle,

Am. J. Phy'siol. 40: 206, 1916.

22. Lewis, J. K., and Dock, W.: The Origin of Heart Sounds and Their Variations in My'o-

cardia! Disease, J. .A. M. A. 110: 271, 1938.

23. Cohn, .A. E., Cardiovascular System and Blood. In Cowdry', E. V. (editor): Problems of

Ageing, ed. 2, Baltimore, 1942, The Williams & Wilkins Co., pp. 111-138.

24. Wearn, J. T., and Mortiz, .A. R.: "The Incidence and Significance of Blood Vessels in Normal

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Sounds, Am. Heart J. 30: 332, 1945,

HYPERTROPHY OF THE HEART OF UNKNOWN ETIOLOGY IN
YOUNG ADULTS; REPORT OF FOUR CASES
WITH AUTOPSIES

Commander Robert F. Norris, M.C., and Lieutenant Commander Harry
H. PoTE, M.C., United States Naval Reserve

I N ONE year at the Philadelphia Naval Hospital, four men between the ages
of 21 and 30 years, with histories of progressive congestive failure, died of
unexplained hypertrophy and dilatation of the heart. Neither clinically nor
at autopsy was the etiology of the hypertrophy determined. All of them had
been under repeated medical observation for at least two years and at no time,
even before the onset of cardiac symptoms, was there any evidence of hyper-
tension or of other factors which commonly result in hypertrophy of the heart.
At autopsy, there was no valvular disease and the large and small coronary
arteries were considered normal for this age. Hypertrophy of individual muscle
fibers was the most conspicuous microscopic abnormality. There was evidence
of focal degeneration of the myocardium, but the lesions were not so extensive
as to constitute a diffuse myocarditis.

Although cases of unexplained sudden death presumably of cardiac origin
during this period of life are occasionally seen at autopsy, particularly by coroner’s
physicians, hypertrophy of the heart in the absence of anatomic defects is usually
not pronounced. In the present cases, however, death, although at first un-
expected, was not sudden except in one patient (Case 2), occurred only after pro-
gressive congestive failure, and was associated with distinct hypertrophy of the
heart. In older patients, clinically unexplained congestive failure and hyper-
trophy of the heart are usually ascribed to a previously unrecognized hypertension
or to arteriosclerosis of the smaller coronary arteries and arterioles. In none
of the cases to be described was there any evidence of either of these factors.

In 1933, Levy and Rousselot^ reported three cases of similar age which re-
semble ours, but found only two others^'® in the literature. In 1937 Levy and
Von Glahn^ reported eight cases from 29 to 66 years of age. Since that time, we-
have found no further reports. In view of the rarity of unexplained hypertrophy
of the heart in the third decade, therefore, a report of four such cases is justified.

Novr at the William Pepper Laboratory of Clinical Medicine. University of Pennsylvania, Phila-
delphia, Pa.

The opinions or assertions contained herein are the private ones of the writers and are not to be
construed as official or reflecting the views of the Navy Department or the naval service at large.
Received for publication April 10, 194G.

599

AMERICAN HEART JOURNAL

ono

REPORT OF CASES
i

< , //i'/’f-v - J. U.. a white man, aged 2S years, was admitted to the Philadelphia Naval

fi. . II \!!e o' 1944 . complaining of shortness of breath and swelling of ankles of about three

‘ The family and past medical histories were irrelevant. He enlisted in the

S' Guard on .April 19, 1940, and had no overseas duty. He was apparently

!7. 1942. .At this time an appendectomy with drainage was performed for gan-
U'U ntiiciti"^. He had no further abdominal complications and the incision healed satis-
( )n the fourth postoperative day, he had fever and cough and was thought to have
hut this u as not confirmed since no x-ray examination of the chest was made. These

• . 1 - subsided in a few days, however, without the administration of sulfonamides. An
•I’m Ilf tiu- chest on the twelfth postoperative day showed no evidence of pneumonia but

' i.\. 'I’e heart to be symmetrically enlarged. Without further study, he was discharged to
> . n Div 12, 1942, the eighteenth postoperative day. On Jan. 4, 1943, becayse of exertional

. e ii.i! pain and palpitation of three daj’s’ duration, he was readmitted to a hospital. Except

in < nlarged heart, no significant findings were reported on ph^-sical examination. He was
<1 SI ii.e ..id fiorn the service because of heart disease on Feb. 12, 1943. The highest blood pres-
-e as 120/90, He was always afebrile.

! ' iilow ing ilischarge he was asymptomaticand was able to work as a packer for nearly eighteen

■ 1 During this period he was examined frequently at a Veterans’ Administration facilit\i,
I n>’ furtlier abnormalities were discovered. On July 18, 1944, however, he noticed shortness
.• huMth and on the advice of a family physician he stopped work. The dyspnea persisted, even
uliile at re^t, and on August 9, he coughed up blood-tinged sputum and noticed that his ankles
.'lie swollen. He was admitted for the first time to this hospital on the same day.

On admission he was cyanotic and orthopncic. The legs were markedly edematous. The
he.iit was greatly enlarged, the rhythm was regular, and the heart rate was 124 per minute.
1 here were no murmurs. Blood pressure was 100 systolic, but the diastolic was not determined.
Numerous r.llea were heard over the lungs and the liver was enlarged three fingerbreadths below
I hi light costal margin. He grew progressively worse and died on Sept. 11, 1944, thirty-three
(ia\'> after admis.sion.

LnhoTalory Data. — During hospitalization for appendectomy, no electrocardiogram was
made. On the .second admission, an electrocardiogram w'as reported as normal. On final ad-
mis'-ion, an electrocardiogram before digitalis was given showed left-axis deviation, QRS intenml
of (1.16 second, indicating bundle-branch block, elevation of RS-T segment in Leads H and HI
.iml depres'iion in Lead CF<, and inversion of T waves in Lead I (Fig. 1). At the time of the
appendectomy, there was a transient leucocytosis, and shortly before death the white blood count
was 33. (Kin. of which 91 per cent wore polymorphonuclear neutrophiles. .A sedimentation rate
was not determined at this time but was preHously normal. Other laboratory data, including
nrinnhsis, red blood cell count, hemoglobin, blood Kahn, and blood urea nitrogen w’crc within
normal limits.

Autapsy {No. 44-182).—

Anatomical Diaznosis: There were hypertrophy and slight focal scarring of myocardium;
maiked dilatation of all chambers of heart; chronic passive congestion of the lungs and liver;
lobular pneumonia; slight atherosclerosis of the aorta; former operative removal of the appendix;
•and an operative scar in the right lower quadrant of abdomen.

Body: 1 he body and the individual organs grossly and microscopically showed extensive
chronic fia'isive congestion, but there were no other relevant lesions except for terminal pneumonia.

Heart:* riie heart w’eighcd 890 grams. The myocardium of both ventricles was hyper-
trophied but there were no focal lesions. Both'auricles and ventricles were greatly dilated.
Altliouch the valves were all thin and delicate, the endocardium of the left auricle was opaque and

jj hi-arts of all casi-s irrossly showed only hypertrophy and dilatation. photORrajihs are not

lY OF HEART OF UNICNOWN ETIOLOGY 601

anary arteries were patent. Only very small athero-
a.

including both ventricles, both auricles, and the mitral
nflammation. The muscle fibers of the left ventricle
the left auricle and ventricle were also increased in
ig were present in the left ventricle but not elsewhere
of the coronary arteries were normal.

1.— Cai
n Lead
■ancli b

ations; QRS interval of 0.16 second; ele^^ation of RS-T
Lead lY; and inversion of T waves in Lead I; probable

m2

AMERICAN HEART JOURNAL

CAf 2.—

air.ki! JH'!ory.—E. P. M., a white man, aged 21 years, was admitted to the Philadelphia
N;n-n! ilo-pita! on Atig. 22. 1944, complaining of severe pain in the chest of a few hours’ duration.
'V»u 'f.!snil>, and past medical histories were irrelevant. He enlisted in the United States Army
timr prior to July. 1942. He had no ot'crscas duty. He was apparently well until some
in jun. . 104.L whtm he had a “cold" which was followed by cough, weakness, and dyspnea
• , %. • t ion. The cuuijh subsided but the weakness and dyspnea continued and he began to lose
.i. I \^ u.i- admitted to the sick list because of these symptoms on July 14, 1943. At

tha! t i!!( , tlu un!v abnormalities, on ph\-sical examination, were pallor and small blood clots
t!i t ' lui-opharyn.':. He was found to have a severe anemia which was considered to be hypo-
<)ri ni l and either microcytic or normocytic Following one transfusion with whole blood and
;r, lUnent with liver c.xtract, iron, and multiple vitamins, the blood count rapidly returned to
noiin.il and he \\a« discharged to duty on Sept. 3, 1943. He was well until about the middle
..f ! >. cvmbu of the same year, when the symptoms of weakness and susceptibility to fatigue re-
! ortK <1 .ind persisted until the time of his second admiss'on on Jan. 5, 1944. He had lost about
fiiti ( n pounds -ince his discharge and again was pale and anemic. Treatment with whole blood
tr.in'‘U'ion-, liver extract, iron, and multiple vitamins was again effective, but whenever this
u\’ mi II wa.v discontinued the anemia recurred. At this time an x-ray film o.*' the chest showed a
mrir.al eardiof horacic ratio, but the heart appeared to have enlarged when compared with the
(..I'll , .11 silhouette of July, 1943. Since there was also electrocardiographic exndence of myocardial
I *i.iiu;e. he was discharged from the service on April 8, 1944. .At this time he had a normal blood
( ouni and was asxunptomatic. During the periods of hospitalization, the blood pressure was
never above 1 10/85. He was always afebrile.

FoUcueiug Ins discharge he had worked regularly and remained well until Aug, 22. 1944, when
he was admitted to this hospital because of sudden, severe, persistent precordial pain.

On admission he was cyanotic and orthopncic. The ankles were moderately edematous; the
heart wa'- moderately enlarged, the rhythm was regular, the rate was 112, and a soft systolic
nuumitr was localized at the apex. The blood pressure was 110/85. Many rfflcs were heard
over both lungs, and the liver was easily palpable. He did not improve and died eight hours
after admission.

Lahnralory Data . — .At the time of the first admission, the red blood cell count was 1,860,000,
anti the hemoglobin was 34 per cent. The volume index was 0.86 and the hematocrit was 13.
1 here was marked hypochromia and poikilocytosis, but no macrocytes or nucleated red cells were
reported. The count was normal on discharge. On the second admission, the red cell count
was 2,700,000 with a hemoglobin of 42 per cent. Thereafter it varied somewhat between these
figures and normal but was normal on discharge in April. On the day of death the red cell count
was 4,410,000, but the hemoglobin was 11.5 grams. Before discharge from the service, repeated
electrocardiograms showed a left bundle-branch block, the time of which was 0.16 second. On
the <!ay of death an electrocardiogram also showed a QRS complex of 0.16 second and low to
inverted T waves in the limb leads (Fig. 2). All other laboratory data during the various periods
of hospitalization were within normal limits. These included sedimentation rates, urinalyses,
white blood and differential counts, blood sugar and cholesterol, blood Kahns, and basal meta-
bolic rates.

Aiik>p.cy (Ao. •}4-]96).—

Aiialnitiiral D:agnosis: There were history of chronic hypochromic anemia (etiology undc-
terruinrti) : erythroid hyperplasia of bone marrow*, hypertrophy and dilation of heart; minute
foc.ll necro-ie.s and scars in the left ventricle of the heart; chronic passive congestion of the lungs,
liver, spleen, and remaining organs; hydropericardium ; bloody pleural effusion (bilateral) ; ascites;
peripheral edema; acute phlebitis of the thyroid vein; multiple thrombotic emboli to the lungs;
and multiple infarcts of the lungs.

Body: 1 here was moderate pitting edema of the dependent portions of the body. On
section. 590 c.c. of blood-tinged fluid were present in the left pleural cav'ity and 300 c.c. in the
right. In the peritoneal cavity there were 300 c.c. of clear straw-colored fluid. There was cx-

NORRIS AND POTE : HYPERTROPHY OF HEART OF UNKNOWN ETIOLOGY 603

tensive chronic passive congestion of all organs. A small vein external to the capsule of the thy-
roid was occluded by a thrombus which microscopically was necrotic. Several of the arteries in
the lower lobes of both lungs were also occluded by thrombi, which sho\ved no evidence of organi-
zation microscopically and which were associated with numerous fresh hemorrhagic infarcts of
the lungs. In sections of the ribs and vertebra! bodies, the erythropoietic elements were in-
creased in number but were otherwise normal.

Fig. 2. — Case 2. The QRS interval is 0.16 second in both tracings; on the day of

death there are T wave changes.

Heart: The heart weighed 560 grams and the pericardial sac contained 120 c.c. of clear
straw-colored fluid. On section of the heart, all of the chambers were dilated and filled with
blood. The left ventricle was distinctly hypertrophied but no focal lesions were seen. The valves
were all thin and delicate and showed no lesions. The coronary arteries were patent and there
were no gross atheromatous plaques in the intima.

Microscopically, numerous sections from both ventricles and the mitral and aortic valves
were examined. The myocardium of the left ventricle was diffusely hypertrophied and the endo-
cardium of the left auricle showed patchy fibrous thickening. Scattered in the left ventricle ivere
occasional stellate scars associated with small amounts of round-cell infiltration. In addition
.-several minute focal necroses together with a few polymorphonuclear leucocytes and lymphocytes
were seen. Similar areas of acute inflammatory reaction were seen in the endocardium of'the

AMERICAN' HEART JOURNAL

cm

k-fi vcfitncif.

rardiinii. Th,.

Thert’ were also small area? of necrosis and fibrinoid degeneration of the endo-
fniall hranciie? of the coronary arteries, however, showed no lesions. No other

ahnorm.ihtie' v. ere seen.

3 .-

Ihs!orv.—H. P. E., a Negro man, aged 25 years, was admitted to the Philadelphia
\ -..il H.i'i'itnl on Jan. 1, 1945. with a chief complaint of periodic shortness of breath. He had
, i' -'t i HI the United States Navy on April 4, 1938. The past medical and family histories were
! rerrn.itive. He had no illnesses Other than minor infections of the upper respiratory tract
I...;. ire ill' lir'-l admission to the sick list.

< >11 \iig. S. 1944, while engaged in heavy work on one of the tropical islands in the South
i‘,i' M- ulu re he had been stationed for several months, he suddenh' fell unconscious. He soon
ri.M.n. d con'-ciousnc-'-s, but on admission to the hospital he was objectively dyspneic, and the
l-hs~ual "ij.ins were not relieved by the administration of adrenalin and aminophylline. An
> !.i\ ii]m of the che.st was normal. He gradually improved, although attacks of dyspnea and
« uiieh tccnrred, and he was evacuated to a hospital in the continental United States. After his
arrn.i!. he had no further dyspnea or other symptoms and was discharged to duty on Dec. 24,
1044 The highest blood pressure during this period was 106/70. Six days later, however, par-
ow-nuil d\ spnea recurred and he was admitted to this hospital the next day, Jan. 1, 1945.

(hi admi.ssion he was dyspneic, and numerous crackling and sonorous rfiles were heard over
ln’th lungs. The heart was not thought to be enlarged; the rhythm was regular, the rate was
72. ,uul no abnormal sounds were heard. Blood pressure was 98/56. No other physical abnor-
malities were noted. Within four days, dyspnea at rest subsided, but the exercise tolerance
appeared to be less than normal. However, he had no other symptoms until March 7, when
he acquired an acute gonococcus urethritis which was satisfactorily treated with penicillin and
which did not recur. On March 11, dyspnea while at rest again appeared and edema of the
ankles was first observed. From that time until death, symptoms and signs of congestive failure
increased in severity, and the heart, b\' physical and x-ray examination, increased in size. Two
days before death he had severe hemoptysis and there were signs of consolidation in both lungs.
He died on June 24, 1945.

Lahoratary Data . — There were no electrocardiograms on the first admission. On the second
admission, repeated electrocardiograms showed constantly changing P-R inter^'als, T waves
var\ ing from flat to the late V type of inversion in all leads, and constantly isoelectric S-T seg-
ments. The cardiac rate varied from 66 to 78 (Fig. 3). Blood cultures on Jan. 2, Jan. 8, Feb.
12, and .-Xpril 16, 1945, were sterile. Except during the episode of urethritis, tests were repeatedly
negative for allergy. Other examinations, most of which were repeated on both admissions, were
also normal, fhese included blood Kahns, blood sugar, blood urea nitrogen, urea clearance,
blood cholesterol, and total scrum protein. Numerous blood smears were negative for malarial
parasites and, in wet preparations of the blood, sickling of the red cells was not demonstrated.

Autopsy (No. 45-194 ). —

A nntomical Diagtwsis: There were chronic degeneration and focal scarring of both ventricles
of heart; hypertro])hy and dilatation of heart; organizing mural thrombi, left ventricle of heart;
chronic passive congestion of lungs, liver, spleen, and kidneys; hydropericardium; hydrothorax,
bilateral; ascites; peripheral edema; extensive lobular pneumonia.

Body: There were generalized subcutaneous edema, most marked in the dependent parts
of the body. On section there were 2,200 c.c. of clear straw-colored fluid in the peritoneal cavity,
200 c.c. in each pleural cavity, and 150 c.c. in the pericardial cavity. The organs all showed ex-
tensive chronic passive congestion. Widespread areas of fresh fibrinopurulent exudate were pres-
ent in both lungs.

Heart: 1 he heart weighed 550 grams. The chambers of the heart were all dilated and filled
with clotted blootl. In the left ventricle, small gray-red mural thrombi were loosely adherent
to the cohmmae carneae. The endocardium of the left ventricle and left auricle was slightly
thickened. The valves were all thin. <le!icate, and apparently normal. The coronary arteries’

NORRIS AND POTE: HYPERTROPHY OF HEART OF UNKNO\W ETIOLOGY

605

were patent and showed only very slight atheromatous changes,
tricles was pale and flabby, but no focal lesions were seen.

The myocardium of both ven-

Microscopically, there was patchy hypertrophy of the left ventricle, but in manv’ areas of
both ventricles the muscle fibers were small and appeared stretched, and small colorless vacuoles
ere numerous in the muscle fibers. In some fibers, the vacuoles were so numerous that a honev-
comb appearance resulted. The fibrous septa were edematous, and rarely minute collections of
lymphocytes, plasma cells, and macrophages were seen. None of these, however, resembled
AschofT bodies. Ihe mural thrombi in the left ventricle were just beginning to organize. In
sections of both auricles and of the mitral and aortic valves, no lesions were seen. Special stains
or glycogen and fat were not obtained since the only available material was preserved in 80 per
cent alcohol. In Gram stains, bacteria were not seen in the thrombi.

I

11

III

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Pjg. 3. — Case 3. Throughout the five months of final hospitalization there were constantly changing
P-R intervals and varying types of T waves in Leads I, II, and IV, which are shown in the above tracings.
The changes in Lead IV may be due to variations in position of the electrodes.

Case 4.-—

Clinical History— C. W., a white man, aged 29 years, was admitted to the Philadelphia
Naval Hospital on June 15, 1945, complaining of vomiting and abdominal pain of four days’
duration. The past medical and family histories tvere irrelevant. He enlisted in the United
States Army in August, 1942, and was tvcll until January, 1945, when he was stationed in Oran,
Algeria. At that time, he was found wandering about the streets in a state of mental confusion'.
Upon hospitalization, a diagnosis of amnesia was made, for which he was discharged from the
service on April 15, after his return to the continental United States. During this period, an

606

AMl-RICAX HEART JOURNAL

x-rav film of tho cht-.=c was reported as normal and the highest blood pressure was 116/80. Ho
tlit-n worked as a bellboy until June 11, 1945, when he was taken ill with nausea, vomiting, and
cramphke abdominal pains, and was admitted to this hospital four days later.

On admi'^sion, he \vas dyspneic, cyanotic, and jaundiced. There was no peripheral edema,
but the superficial veins of tlie neck were distended. The heart appeared to be moderately
enlarged, both on plnsical and subsequent x-ray examination; the cardiac rate was 120; the
rii’. thin was regular; audible gallop .sounds were present ; and a soft systolic murmur was localized
at the apex. The blood pressure was 90/82. The lungs were net remarkable and the liver and
spleen were not at first palpable. Within a day, however, he became mentally confused ; numerous
crackling rfile^ were heard over both lungs; signs of effusion in the pleural and peritoneal cavities
appeared ; and the legs became edematous. The jaundice deepened and the liver became palpable.
He grew weaker and died on June 24, 1945, nine days after admission.

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Kl'.;. -1. — Case 4. This tracing taken during the terminal stage of illnass shows low voltage QRS com-
plexes in limb leads and the flattened Ti.

Laboratory Data. On the first admission, electrocardiograms were reported as norma).
During the final hospitalization, an electrocardiogram showed a P-R interval of 0.18 second;
a QRS complex of 0.07 second and low voltage throughout; and flattened T waves in all leads
(Fig. 4). During the first admission, all laboratory tests were norma! including repeated smears
for malaria, blood Kahns, blood counts, urinalyses, examination of the spina! fluid, electroenceph-
alogram, blood sugar and urea nitrogen, and several basal metabolic rates. During his final ill-
ness, nr.nah-scs showed the presence of bile, traces of albumin, and numerous wiiite blood cells.
1 he blood bilirubin, estimated by the van den Bergh method, was 9 mg. per 100 cubic centimeter,
pie blood urea nitrogen rose from 18 on admission to 82 mg. per 100 c.c. on the day before death.
One blood culture was sterile.

NORRIS AND POTE : HYPERTROPHY OF. HEART OF UNKNOWN ETIOLOGY 607

Autopsy {No. 45-197 )'. —

Anatomical Diagnosis: There were chronic degeneration of both ventricles of heart; hypertro-
phy and dilatation of heart ; chronic passive congestion of lungs, spleen, liver, and kidneys ; hydro-
thorax, bilateral; ascites; peripheral edema; jaundice; organizing mural thrombi, left vertricle
of the heart; embolic thrombus and infarct of the left kidney; organizing thrombi of the prostatic
veins; multiple emdolic thrombi of the pulmonary arteries; and multiple infarcts of both lungs.

Body: The lips, mucous membranes, and nail beds were intenselj’^ cyanotic. The legs, de-
pendent parts of the body, and the eyelids were edematous. The skin and sclerae were jaundiced.
On section, 1,000 c.c. of clear, bile-tinged fluid was present in the abdominal cavitj^, 1,500 c.c.
in the right pleural cavity, and 300 c.c. in the left pleural cavity. The amount of pericardial fluid
was not significantly increased. There was marked chronic passive congestion of the organs.
A recent small infarct was present in the left kidney. Most of the veins about the prostate were
occluded by organizing thrombi. Large hemorrhagic infarcts were present in both lungs and were
associated with numerous organizing thrombi in the pulmonary arteries. The liver was markedly
engorged with blood and microscopically the central and mid-zonal areas were necrotic and re-
placed by hemorrhage. Permission was not obtained to examine the brain.

Heart: The heart weighed 450 grams. All of the chambers of the heart were dilated and
filled with blood. The left ventricle also was moderately hypertrophied. The valves were all
normal. Among the trabeculae of the left ventricle were several small gray-red thrombi which
were firmly attached to the underlying endocardium. Elsewhere the endocardium was normal
and there were no gross lesions of the myocardium. The coronary arteries were patent and
showed only very slight atheromatous changes of the intima.

Microscopically, in sections of both ventricles, groups of muscle fibers, particularly in the left
ventricle, were hypertrophied. In most areas, howev'er, the individual fibers were thin and ap-
peared stretched. A few of the hypertrophied fibers contained scattered, clear, colorless elliptical
vacuoles within the cytoplasm. This vacuolization was perhaps more conspicuous beneath the
endocardium to which were attached the mural thrombi. These thrombi were already deeply
invaded by proliferating fibroblasts and lamination was still visible only on the surface. Else-
where the endocardium was normal. No lesions were seen in either auricle or in sections of the
mitral and aortic valves. Since onl}' blocks preserved in 80 per cent alcohol were available,
stains for glycogen and fat were unsatisfactory'. In Gram stains bacteria were not seen in the
thrombi.

DISCUSSION

In a discussion of these cases, it is advisable first to recapitulate the salient
clinical features in order to emphasize their differences.

In Case 1, hypertrophy of the heart and symptoms of myocardial insufficiency
were first detected soon after an operation for gangrenous appendicities requiring
drainage. Convalescence was complicated only by a respiratory tract infection,
thought to be pneumonia, which subsided without the administration of sul-
fonamides. The patient had no further evidence of infection and was afebrile
until shortly before death, when bronchopneumonia occurred. Following dis-
charge from the service, because of enlargement of the heart, for which hospitaliza-
tion was not considered essential, he was examined frequently as an outpatient,
but evidence of congestive failure was not recognized until the final admission
to this hospital eighteen months aftenvard and one month before death. In
Case 2, congestive heart failure was not recognized until the final admission a few
hours before death. The disorder for which the patient was first admitted to the
sick list and for which he was subsequently discharged from the service was un-

AMERICAN heart JOURNAL

explained recurrent hypochromic anemia which always responded promptly
to treatment. However, the patient himself related the onset of sx’mptoms
to an acute infection of the respiratory tract, but this infection was not observed
rhnicaliy and he remained afebrile throughout the illness. Laboratory data
abo did not suggest the presence of infection. At first, in Case 3, the patient was
'houeht to have bronchial asthma, and it is possible that he also had acute
f winchilis. E.vcept during the attack of acute urethritis, he had no further evi-
<!( nee of infection and was afebrile until the occurrence of terminal broncho-
pneumonia. The diagnosis of bronchial asthma was subsequently discarded
u iien no ex'idence of allergy was demonstrated. For at least six months before
de.uli, however, incipient congestive failure was recognized clinically and for
this reason he was not discharged from the servdee. In Case 4, the patient was
firt .1 ho.spitalized for amnesia of sudden onset and was subsequently discharged
with this diagnosis. Two months later, however, he was admitted to this
h(!-pital in severe congestive failure and died nine days later. The clinical
i.iin.'-e was entirely afebrile and laboratory data did not suggest the presence
oi ,in infectious disease.

At this point, parenthetically, it is wwthy of emphasis that at autops}’’
the mural thrombi in the left ventricles of Cases 3 and 4 did not resemble the
vegetations of bacterial endocarditis. Grossly the surfaces were smooth. The
deeper layers, microscopically, were being replaced by fibroblasts and the super-
ficial layers were laminated and not necrotic. Bacteria could not be demon-
strated with Gram stains. It is evident, therefore, that only in Case 1 tvas the
omset of .symptoms related to the occurrence of an acute infectious disease and
in none of the cases w'as there evidence of any chronic infection. It is equall}'
apparent that the onset of illness and clinical course in each case differed and did
not at first suggest a diagnosis of heart disease.

It is interesting that in each patient serious heart disease was not at first
recognized as the outstanding abnormality. Only in Case 1 w'as the diagnosis
made early and then only after the patient "was discharged to duty following re-
cover}' from the appendectom}’. In patients of this age, without hypertension
or ex'idence of valvular disease, a diagnosis of heart disease is not ordinarily a
prominent consideration. However, in all cases, a thorough survey of the heart
w.-xs actually made early in the course of the illness. That tests, including elec-
trocardiograms and chest x-ray films, at first gave normal results, e.xcept in Case 1 ,
probably e.\'plains why a diagnosis of heart disease was temporarily discarded.

The question arises, therefore, when during the illness of each patient
heart disease may have occurred. In Case 1, the heart was reported as being
enl.arged b}' x-ray e.vamination during convalescence from the appendectomy,
rhis was confirmed during the second admission, but at that time an electrocard-
iogram was .said to be normal. It is quite possible, therefore, that cardiac en-
largement may ha\'e preceded the appendicitis. In Case 2, enlargement of the
teart by x-ray examination and electrocardiographic changes suggestive of
nn oairdial damage w'ere first recognized six to eight months following the onset

NORRIS AND POTE; HYPERTROPHY OF HEART OF UNKNOWTS^ ETIOLOGY 609

of symptoms. There is a distinct possibility, however, that at the time of the
first admission, when cough, weakness and dyspnea on exertion were conspicuous
symptoms, the patient was already suffering from heart disease. It is also
probable that in Case 3, heart disease was responsible for the paroxysmal attacks
of cough and dyspnea which at first were diagnosed as bronchial asthma. In
Case 4, likewise, the sudden onset of mental confusion less than six months
before death may have been caused by emboli from an already damaged heart.
In this connection, it will be recalled that at autopsy the mural thrombi in the
left ventricle were already extensively organized. From the available evidence,
therefore, it is possible that heart disease in all four cases already existed at the
time of the first admission to the sick list.

There appears to be little doubt, pathologically, that the principal cause
of death in all four cases was congestive heart failure. In the first place, the
hearts weighed 890, 560, 550, and 450 grams, respectively. These weights are
obviously greater than the limits of normal. In the second place, evidence of
marked chronic passive congestion was widespread both grossly and microscopi-
cally. In Cases 1 and 3, however, the final illnesses were complicated by terminal
bronchopneumonia. Multiple pulmonary emboli and infarcts in Cases 2 and 4
were undoubtedly manifestations of peripheral stasis and thrombosis incident
to the congestive failure and almost certainly were important causes in precipi-
tating death.

The jaundice and necrosis of the parenchymal liver cells in Case 4 may
have been due to chronic passive congestion and to the destruction of excessive
amounts of red blood cells in the pulmonary infarcts, or, to these factors plus
an acute infectious hepatitis; the associated uremia was distinctly terminal.

In Cases 3 and 4, the presence of mural thrombi in the left ventricles sug-
gests myocardial infarction, but the coronary arteries grossly and microscopi-
cally were not occluded and even microscopically there were no large areas of
necrosis. It is much more likely that a combination of stasis of blood flow in the
ventricles and small areas of subendocardial degeneration was responsible for
these lesions.

As for etiology, it is apparent from the case reports that none of the factors
commonly responsible for hypertrophy and dilatation of the heart were present.
Thus, there was no evidence of hypertension, coronary arteriosclerosis or throm-
bosis, valvular disease, congenital defects of the heart, or chronic disease of the
lungs. There was no evidence of hyperthyroidism, clinically or pathologically.
As far as can be determined, the diets of the patients were adequate and in some
instances were supplemented with multiple vitamin preparations. It is very un-
likely, therefore, that any of them were suffering from vitamin B deficiency.
The possibility of rheumatic myocarditis without valvulitis was considered, but
the clinical manifestations of rheumatic fever were lacking and the small foci
of round-cell infiltration in the ventricles of Cases 2 and 3 did not resemble
Aschoff bodies.

In Case 2, there was recurrent, moderately severe anemia, which was the
presenting symptom during most of the illness. It was classified only as being

AMERICAN* HEART JOURJTAE

rtlO

hypochromic and the etiology was not determined. The response to therapy
was pronipl, however, and the patient was not severely anemic at death. There
is great doubt, therefore, whether an anemia of this extent so affected the heart
.IS to anise ht’pertroph}' and congestive failure. White^ believed such anemias
to be without effect in permanently damaging the heart unless they were severe
Mr prolonged. Nemet and Gross® found cardiac hypertrophy to be extremely
1 ..-e in anemia. Amadeo" was equally impressed by the failure of anemia to
produce cardiac hypertrophy.

Recenth’ Candel and Wheelock® have emphasized the frequency with which
.icute infections, particularly of the respiratory tract, may be complicated by
transient acute myocarditis and have described the electrocardiographic changes
which are thought to indicate derangement of the myocardium. But in our cases
electrocardiograms were not significantly abnormal early in the illnesses. How-
ever, the onset of symptoms in Case 1 did immediately follow an acute infection.
I ndoubtedly, the remaining patients had upper respiratory tract infections from
tjine to time before the onset of the final illness, but these must have been so
mild that hospitalization was unnecessarJ^ The attack of urethritis in Case 3,
moreover, occurred long after the onset of cardiac symptoms and, although it
ma\' have adversely affected the course of the illness, it certainly was not the cause
of it. It is possible that the apparent myocardial damage described by Candel
and Wheelock® ma}* not alwaj's be reversible and may cause cardiac hypertrophy
some time afterward; but this concept is so unusual that it can be considered
only ns a possibility at this time.

Although the present cases are not typical of so-called isolated myocarditis
of Fiedler® in which extensive inflammation of the myocardium is characteristic,
there are points of similarit}'^ between the two groups which might justify tliis
cla.'ssification of our cases. As in isolated myocarditis, so in the present cases,
relati\ ely rapid and progressive enlargement of the heart terminated in congestive
failure, but evidence of chronic infection was lacking.

In Cases 2 and 3, there were minute, although rare, foci of inflammation in the
mj'ocardium, and in Cases 3 and 4, there was also extensive focal vacuolization
of the myocardium of the ventricles. These were not so extensive, however, as
to constitute an unequivocal diffuse myocarditis, and in Case 1 there was neither
vacuolization nor inflammatory exudate. In this case, furthermore, the scarring
was no more extensive than is customarily obseiw’^ed in myocardial hypertrophy
of this degree from any common cause. Nevertheless, it may be argued that
extensive inflammalorj'^ exudate was present in the myocardium of the present
cases earlier in the course of the disease and had largely disappeared by the time
of death. Even if these cases are thought to belong in this group, therefore, one
is still far from any conclusion as to etiolog>^ In his recent reviews of the
literature, Saphiri®'” has pointed out not only the variability of e.xtent and
character of the inflammatory exudate in the hearts of the reported cases of iso-
lated myocarditis, but also the large number of infections which have been sug-
gested as dubious causes of the disease. Fiedler’s myocarditis, consequently,

NORRIS AND POTE; HYPERTROPHY OF HEART OF UNICNOWN ETIOLOGY 611

appears to be a group which includes various disease entities, the etiology of
which is just as uncertain as that of the present cases.

It is unfortunate that properly fixed material was not available for glycogen
or fat stains in Cases 3 and 4. Although it is highly unlikely that the vacuoles
in the muscle fibers were glycogen, or that these cases represent some phase of
glycogen-storage disease, it would be satisfying to settle this question. If the
lesions were either fatty or hydropic degeneration, as seems more likely, such
abnormalities are not specific of any disease entity. Interesting!}^ enough, one
of Levy and Rousselot’s^ cases also had extensive vacuolization of the myocardium
which was interpreted as hydropic degeneration.

From the preceding discussion, it is evident, therefore, that the cause of the
myocardial hypertrophy in each of the four cases presented is obscure, and
etiologically these cases may be wholly unrelated.

SUMMARY

, 1. Four fatal cases of unexplained hypertrophy and dilatation of the heart
during the third decade of life are presented. None of the usual causes of hyper-
trophy were present.

2. The onset of illness differed in individual cases and was not at first recog-
nized as heart disease.

3. Electrocardiograms at first were normal. When changes occurred,
the abnormalities suggested only nonspecific myocardial damage.

4. ' The possible etiologic factors are discussed, but it is not concluded which,
if any, were responsible for the cardiac hypertrophy.

5. There is no certainty that the causes of heart disease in the four cases
were related.

REFERENCES

1. Levy, R. L., and Rousselot, L. M.: Cardiac Hypertrophy of Unknown Etiology in Young

Adults, Am. Heart J. 9: 178, 1933.

2. Whittle, C. H.: “Idiopathic” Hypertrophy of the Heart in a Young Man, Lancet 216:

1354, 1929.

3. Laubry, C., and Walser, J.; Sur un cas d’insuffisance cardiaque primitive: les myocardies.

Bull, et mem. Soc. med. d. hop. de Paris 49; 409, 1925.

4. Levy, R. L., and von Glahn, W. C.; Cardiac Hypertrophy of Unknown Etiologj' in Adults,

Tr. A. Am. Physicians 52; 259, 1937.

5. White, P. D.; “Heart Disease”, ed. 2, New York, 1937, The MacMillen Co., p. 389.

6. Nemet, G., and Gross, H.; Cardiac Hypertrophy in a Case of Cooley’s Anemia, Am. He.art

J. 12; 352, 1936.

7. Amadeo, J. A.: Un Nuevo Fenomeno Cardiologico observado entre los Campesinos Puertor-

riquenos; Analizado a Traves de los Llamados Soplos Hemicos; Y una Nueva Teoria
que de una Explicacion Fisio-Anatomica Razonable de Esta, Bol. Asoc. med. de
Puerto Rico 37: 161, 1945.

8. Candel, S., and Wheelock, M. C.; Acute Non-Specific Myocarditis, Ann. Int. Med. 23;

309, 1945.

9. Fiedler: Ueber akute interstitielle Myocarditis, in Festschrift des Stadtkrankenhauses,

Dresden, 1899, Friedrichstadt; cited by Saphir (1941).

10. Saphir, 0.: Myocarditis (A General Review, With Analysis of Two Hundred Forty Cases),

Arch. Path. 32: 1000, 1941.

11. Saphir, O.: Myocarditis (A General Review, With Analvsis of Two Hundred Forty Cases),

Arch. Path. 33: 88, 1942.

PARENTERAL \'ITAMIN B AS AN AGENT FOR DETERMINING THE
ARM-TO-TONGUE CIRCULATION TIME

Part I

Roy E. Swenson, M.D
Pittsburgh, Pa.

P REMOL’S observations on the velocity of blood flow have been made by
using saccharine,'* calcium salts and magnesium sulfate,® and decholin®
to determine the arm-to-tongue circulation time. Sodium cyanide*- and alpha
lobeline-’*"*'*'** have been used to measure the circulation time from the arm
to the carotid sinus. Ether- •" has been used to determine the circulation time
from the arm to the lung. Papaverine® has been utilized to measure the circula-
tion time frotn the arm to the central nervous system.

The arm-to-tongue circulation time is of clinical value® in the diagnosis of
congestive heart failure and of those diseases in which the venous return is
obstructed. It is also of value in those diseases where the velocity of the blood
flow is increa.sed, as in the anemias, hyperthyroidism, and certain febrile states.

Hussey, Cyr, and Katz® have summarized the requirements for a suitable
agent for determining the circulation time as follows:

1. It must he nbnto'dc in the dosage used.

2. It must have no undesirable efTect upon the condition being studied.

3. There must be a minimum of unpleasant side effects.

4. It must be eliminated rapidly so that it can be used repeatedly.

5. It must have an end point that is easily recognized by the patient.

G. It should be readily available at a low price.

The results of the work to be reported indicate that the vitamin B complex when
given intravenously meets all of these conditions.

The use of the vitamin B complex as an agent to determine the arm-to-
tongue circulation lime was suggested when the complex was given intravenously
to an obstetric patient three days post partum. She complained of a taste
on her tongue similar to that of a “chewed-up vitamin tablet.” The comple.x
was then given to other patients who also tasted it. These observations led
to further study of its \*alue in estimating circulation lime.

for inititiKition March 12, 1910.

i-Tt *’1 Mercy IIo^pUaK

612

SWENSON : PARENTERAL VITAMIN B AND ARM-TO-TONGUE CIRCULATION TIME 613
The preparation used in this study had the following composition* ;

Thiamine hydrochloride 10.0 mg.

Riboflavin 10.0 mg.

Pyridoxine hydrochloride 5.0 mg.

Calcium pantothenate 50.0 mg.

Nicotinamide 250.0 mg.

These amounts were contained in 5.0 c.c. of sterile isotonic saline solution.
Five cubic centimeters were used for each determination. A duplicate deter-
mination was made within a few seconds of the initial one. Each subject,
therefore, received a total of twice the amount of the drugs listed.

The normal serum concentration of thiamine hydrochloride is from 0.2
to 2.0 fxg per 100 c.c.,^'‘ and the intravenous administration of 50 mg. of the
substance elevates this level to from 130 to 200 /xg within five minutes. This
falls to from 5 to 15 fig within an hour, for the substance is almost immedi-
ately excreted. Large doses have been given to rats and dogs without any
toxic effect being noted in the electrocardiograms.® From 26 to 68 per cent of a
16 mg. test dose of riboflavin given intravenously is excreted within four hours,
and there is little storage of the substance.'®’'^ Pyridoxine hydrochloride and cal-
cium pantothenate are rapidly excreted.^® The intravenous administration of
5 mg. of nicotinic acid per kilogram in man increases the normal whole blood
concentration from 0.25 to 0.89 mg. per 100 c.c. to a maximum of 130 mg. per
cent; this falls to normal in two hours as conjugates are excreted in the urine.^^’^®
In the literature reviewed, no variations in the pulse or blood pressure were re-
ported after the administration of these substances in the dosages given.

TECHNIQUE

The patient was placed in a semirecumbent position and the left arm was
supported at the approximate level of the right auricle. A tourniquet was then
applied above the antecubital fossa. Sterile 10 c.c. syringes and No. 20 needles
were used. After the needle was inserted into one of the antecubital veins, the
tourniquet loosened, and venous flow re-established, 5 c.c. of the solution were
rapidly injected. Time was started on a stop watch at the beginning of the
injection. When the patient stated that he tasted the substance, time was
stopped, but the needle was left in the vein. When he no longer tasted the sub-
stance, a duplicate determination was made and the needle removed.

The taste on the tongue was described as follows:

1. A taste like that of a brewers' yeast tablet.

2. A taste similar to that of a vitamin tablet.

3. A stale, fishy taste and odor.

4. A warm sensation on the tongue and in the throat.

Interns and nurses who received the substance stated that the taste and odor
were unmistakable and that the onset of the taste was abrupt and intense.

*The commercial preparation, “Solu-B,” manufactured by The Upjohn Co., Kalamazoo Mich
was used. The Upjohn Company generously supplied tlie Solu-B used in this work.

AMERICAN HEART JOURNAL

6hi

RESULTS

Obviously this test would have more practical value and the observations
reported would be of greater scientific interest if it could be established that a
single component produces the taste sensation. Further study of this aspect
of the problem is in progress.

Arm-to-tongue circulation times were determined on fifty normal subjects
from various age groups. No circulatory abnormalities were recognized or
suspected in any of them. Table I summarizes the control group. The average
limes of the fifty control subjects as a single group varied from 9.8 to 10.3
seconds for the initial and duplicate determinations, respectively.

Tari.e I. Average Arm-to-Toxgue Circulation Times of Norm.al Controls

NUMBER OF
PATIENTS

AGE GROUP

IN YEARS

CIRCULATION TIME IN SECONDS

DEVIATIONS IN SECONDS

FIRST

DUPLICATE

FIRST

DUPLICATE

16

16-30

8.7

9.7

-2. +4

±3

16

30-40

10. I

10.5

±4

18

40-

10.7

10.7

±3.3

±3

Estimates of circulation time were made on fifty-two patients with cardiac
disease. The cases were studied in four groups. Table II summarizes the
results obtained in three groups in which congestive failure was present. Table
III summarizes the fourth group in which there was heart disease without
congestive failure.

Table II. .Average Arm-to-Tongue Circulation Times of Patients
With Congestive Failures

number of

PATIENTS

DISEASE PROCESS

CIRCULATION TIME IN j

SECONDS

DEVIATIONS IN RANGE IN
SECONDS

FIRST

1 1

DUPLICATE

[ FIRST

DUPLICATE

15

Congestive failure; no
! treatment

34.8

i

34.6

28-53

27-49

14

1

i Congestive failure;

digitalized but not i
controlled*

22.7

23.1

14.1-46.7

13.. 5-39. 9

10 i

Congestive failure; j

digitalized and con- ’
trolledt

11.8

11.8

9.8-13.4

9.0-15.1

*l’atlPti{>! had only 0.7 Om. of digitalis,

iratirnts had rccclvwl at lc.ast 1.4 Gm. of digitalis.

SWENSON : PARENTERAL VITAMIN B AND ARM-TO-TONGUE CIRCULATION TIME 615

Table III. Arm-to-Tongue Circulation Times of Patients With Cardiac Disease But

Without Congestive Heart Failure

1 ■ '

1

CIRCULATION TIME

case

DISEASE

FIRST

DUPLICATE

• 1

S. B. E.; mitral stenosis

10.1

10.2

2

S. B. E.; mitral stenosis

12.5

14.3

1

3

Hypertension

9.9

10.8

.4

Constrictive pericarditis, after pericardiectomy

12.2

10.0

5

Hypertension; auricular fibrillation

17.0

21.5

6 1

Coronary occlusion after two weeks

10.0

10. 0

7

Hypertensive heart disease; cerebrovascular accident

16.2

15.6

s

Hypertensive encephalopathy; hypertension

9.1

9.4

9

Coronary occlusion

20.0

23.4

10

.Vteriosclerosis heart disease; auricular fibrillation;
digitalized

10.3

11. 0

11

Arteriosclerosis, hypertension: auricular fibrillation; ven-
tricular aneurysm

19.2

16.8

12

Hypertension ; aortic stenosis

10.5

12.0

13 ■

Arteriosclerosis: auricular fibrillation

31.0

32.5

The longest circulation times were recorded in those patients in whom
congestive failure was severe and untreated. The times were also increased in
those patients whose failure had been treated but not controlled. Those who
were treated and whose failure had been clinically controlled had times that ap-
proached the normal range, although few were actually within normal limits'

Patients who received this vitamin B preparation had few side reactions. ,
Two complained of epigastric fullness, and four stated that they felt unusually
warm. One patient complained of bladder tenesmus twenty-four hours after
the injection. No other side effects were noted.

SUMMARY

1. The arm-to-tongue circulation time using parenteral vitamin B as
the test agent has been determined on fifty normal subjects. In this control
group the average time was found to vary from 9.8 to 10.3 seconds for the initial
and duplicate determinations, respectively.

2, Similar determinations were also made on a group of fifty-two patients
with cardiac disease. It was found that the circulation times determined by
this method parallel the times reported for other test agents.

616

AMERICAN' HEART JOURNAL

3. The vitamin B preparation used appears to be nontoxic, has little
elYect upon circulatory dynamics, is readily available, is eliminated rapidly,
and has an abrupt end point. The side reactions are minimal. This prepara-
tion. therefore, meets the requirements for a satisfactory agent for the determina-
tion of the arm-to-tongue circulation time.

4. Studies are now being made to determine which components of the B
complex are responsible for the distinctive end point.

.Appreciation is expressed to Dr. \V. L. Mullins, cardiologist of the Mercy Hospital, Pitts-
burgh, Pa., for many helpful suggestions.

REFERENCES

1. Baer, S., and Isard, H. J.: Value of Ether Circulation Time in the Diagnosis of Right

Heart Failure, Am. J. M. Sc. 200: 209, 1940.

2. Berliner, K.: Use of -Alpha Lobeline for Measurement of the Velocity of the Circulation,

Arch. Int. Med. 65: 896, 1940.

Colrell, J. D., and Cuddie, D. C.; Arm to Tongue Circulation Time in Chronic Asthma,
Bril. M. J. 1: 70, 1942.

4. Duras, F. P.: Measurement of the Circulation Time With Saccharin, Lancet 1: 30.3, 1944.
.3. Elek, S. R., and Solarz, S. D.: Use of Papaverine as an Objective Measure of the Circula-
tion Time, -Am. HesVRT J. 24: 821, 1942.

6. Haynes, F. W., and Weiss, S. : Responses of the Normal Heart and the Heart in Experi-

mental Ahhamin Bi Deficiency to Metabolites (Pyruvic Acid, Lactic Acid, Methyl
Glvoxal, Glvceraldehyde and Adenylic Acid) and’ to Thiamine, Am. Heart T. 20:
34, 1940.

7. Hitzig, W. M.: The Use of Ether in Measuring the Circulation Time From the Antecubital

Veins to the Pulmonary’ Capillaries, Am. Heart J. 10: 1080, 1934.

8. Hu.ssey, H. H., Cyr, D. P., and Katz, S.: Comparative Value of Calcium Gluconate, Mag-

nesium Sulfate, and .Alpha Lobeline as .Agents for the Measurement of the Arm to
Tongue Circulation Time in Fifty Patients With and Fifty Patients Without Heart
Failure, Ann. Int. Med. 17: 849, 1942.

9. Hussey, H. H., AVallace, J. J., and Sullivan, J. C.: Value of Combined Measurements of

Pressure on the -Arm to Tongue and Arm to Lung Circulation Times in the Study of
Heart Failure, Am. Heart J. 2.3: 22, 1942.

10. Lillienfcld, A., and Berliner, K.: Duplicate Measurements of the Circulation Time Made

With Alpha Lobeline Mixture, Arch. Int. hied. 69; 739, 1942.

11. Piccione, F. V., and Boyd, L. J.: Determination of Circulatory Velocity by Alpha Lobe-

line, J. Lab. & Clin. Med. 26; 766, 1944.

12. Reingold, 1. M., Neuwelt, F., and Necheles, H.: Circulating Time (Sodium Cj’anide

Method) in Human Beings and the Dog as .AfTccted by Fasting and bv Meals, J.
Lab. & Clin. Med. 28; 812, 1943.

13. Goodman, L., and Gilman, .A.: The Pharmacological Basis of Therapeutics, 1941, The

M.acmillan Co., New A'ork, pp. 12, 54, 1259.

14. Cantarow, .A., and Trumper, M.: Clinical Biochemistry, ed. 3 (revised), Philadelphia and

London. 1945, W, B. Saunders Co., pp. 314-331.

15. Field, H., Melnick, D., Robinson, D., and Wilkinson, C. F.: Studies on the Chemical

Diagno.sis of Pellagra, J. Clin. Investigation 20: 379, 1941.

16. The Physiological Acitivity and Experimental Clinical Use of A’itamin Bt, Rahway, N. J.,

1941, Merck & Co., Inc.

17. The Physiological Activity and Experimental Clinical L^se of Pantothenic -Acid, Rah-

way, N. J., 1941, Merck & Co., Inc.

IS. The Physiology and Clinical Use of Nicotinic Acid and Nicotinamide, Rahway, N. J., 1940.
Merck and Co., Inc.

THE COMBINED USE OF LANATOSIDE C AND.QUINIDINE SULFATE
IN THE ABOLITION OF ESTABLISHED AURICULAR FLUTTER

Ralph M. Tandowsky, M.D., Joseph M. Oyster, M.D., and
Alexander Silverglade, M.D.

Los Angeles, Calif.

D igitalis leaf and qulnidlne have been recommended, singly and in com-
bination, for the abolition of auricular flutter.* We have not obtained
consistent results by this method of therapy. One reason is that this arrhythmia
frequently undergoes spontaneous reversion to a normal mechanism in both
treated and untreated cases. In a study embracing the use of these drugs, this
clinical inconsistency may be greatly obviated by using as test subjects patients
with established auricular flutter who have failed to respond to various methods
of therapy for a period of not less than three days. Furthermore, a better pharma-
cologic understanding of both quinidine and digitalis is essential so that the
careful choice of each in proper dosage and sequence will result in therapeutic
effectiveness. Heretofore, with the exception of auricular fibrillation, the use of
drugs in the conversion of the various arrhythmias has not been based upon
sound therapeutic principles.

The action of both quinidine and digitalis on the heart muscle and its neuro-
mechanism is varied and not without complicating factors. Quinidine, for
example, reduces vagal tone indirectly, while its direct effect is to depress con-
duction in auricular muscle.’ Thus, indirectly it improves conduction and directly
this function is depressed; its paralyzing action on the vagus nerve improves
conduction, while its action on the auricular muscle increases the refractory
period, thus prolonging the duration of the circus wave. A-V conduction under
its influence may be variable,- This variability of quinidine action has led many
to recommend digitalis as the preferable drug in the treatment of supraventricular
tachycardia.® It is through effects such as these that quinidine slows the circus
rate in auricular fibrillation.^’ “ Its action when a mechanism other than auricular
fibrillation is present is difficult to predict. This leads us to believe that the use
of quinidine in the treatment of auricular flutter is unsound therapy, while in the
presence of auricular fibrillation its value has been clearly established.

Digitalis^ on the other hand, exerts a stimulating vagus effect® which shortens
the refractory period. Its direct muscular action slows conduction in auricular
muscle by increasing the refractory period. Vagal action is more marked than
the direct effect on the auricular musculature and the usual result, therefore, is

From tlio Department of Medicine of the College of Medical Evangelists and the Medical Service
of the Los Angeles County General Hospital.

Received for publication Nov. 14, 1945.

617

AMERICAN' HEART JOURNAL

61 S

an increase in the rate and irregularity of the circus movement. In addition
to its effect on the \-agus and the auricles, digitalis produces a slowing effect on
the ventricles by direct and indirect depression of the A-V node. The combined
effects of digitalis are an effect on the refractory period of auricular muscle, which
acts toward converting auricular flutter into auricular fibrillation, and depression
of A-V conduction.®

Lanatoside C* by its strong vagus influence, in our experience has been
c^pecially effectual in slowing the heart rate. Its rapidity of action, in our opinion,
accounts for its strong i-agus effect, and this action is far superior to other forms
of digitalis in common use.^ Rapid slowing of the \'entricular rate has been the
rule in the presence of auricular flutter when lanatoside C is used; of especial
interest has been our frequent observance of the conversion of auricular flutter
to auricular fibrillation following this slowing effect. When slowing of the
heart rate and restoration of normal rhythm occurs, we may attribute this effect
to the combined action of digitalis upon the auricular muscle and nodal tissue.®

Digitalis, particularly when given by the oral route, often fails to produce
effective cardiac response in the presence of auricular flutter and other supra-
ventricular arrhythmias, particularly in the presence of congestii^e heart failure.'®
Improper assimilation from a digestive tract is probably the causati\‘e factor.

Lanatoside C, when given intravenously, has many advantages over oral
digitalis, particularly if immediate action is essential. We ha\’’e demonstrated
its rapid action in auricular flutter, clinically and electrocardiographically, in
tho.se with and without congestive heart failure.'® Lanatoside C, when given
intravenously, will, on occasion, convert auricular flutter to sinus rhythm. This
conversion, however, is inconsistent when this arrhythmia has obtained for
many days. Con^'ersion of auricular flutter to auricular fibrillation by the
intravenous use of lanatoside C is seen quite consistently in those patients whose
auricular flutter has been established for three or rhore daj'-s. Once auricular
fibrillation makes its appearance, the use of quinidine may be of definite thera-
peutic value for the conversion of the arrlij-thmia to sinus rhythm. Lanatoside C
may be given in full therapeutic dosage, quickly, by the intravenous route, with
a minimum of untoward symptoms."’ It has also been shown to be of value
prophylactically when sinus rhythm returns.

METHOD AND PROCEDURE

This study embraces the use of both lanatoside C and quinidine sulfate in
sequence. Lanatoside C was gi\'en intravenously in full digitalizing dosage
(1.6 mg.). The effects were maintained by the administration of 1 mg. dail}-.
Quinidine sulfate was used in varying dosage, depending upon ^ndi^'iduai require-
ments and tolerance (.72 to 1.44 Gm.).

After the diagnosis of auricular flutter was established clinically and electro-
cardiographically, historical data were carefully studied to determine the quan-
tity and type of previous medication. Patients who receiv'ed digitalis in appreci-

Commcrcially nwrkeU'd as Cwlilanid by the Saiidoz Chemical Works. Inc., Now York. N. Y.

TANDOWSKY ET AL.: LANATOSIDE C AND QUINIDINE SULFATE 619

able quantities just prior to admission were eliminated from the series. The
subjects included in this study were chosen irrespective of age, sex, race, and
complicating disease. All were hospitalized. Following the intravenous admin-
istration of lanatoside C, frequent serial electrocardiograms were obtained, and
clinical examination was made at frequent intervals. As soon as the diagnosis
of auricular fibrillation was established, quinidine sulfate was given orally with a
maintenance dosage of lanatoside C. When sinus rhythm, was established, the
quinidine was discontinued but the prophylactic dosage of lanatoside C was
continued. In some of the group, other forms of supportive therapy were used,
depending upon the underlying symptoms and disease.

RESULTS

Sixteen men and five women constituted the series of patients studied
(Table I and Figs. 1, 2, 3, and 4). The diagnosis of auricular flutter was clearly
established by the electrocardiograph in all twenty-one patients. The ventricular
rates ranged from 140 to 200 per minute. The duration of auricular flutter prior
to admission varied from three to twenty-eight days, with an average prethera-
peutic duration of approximately fifteen days. This computation had to be
based mainly upon information given by the patients and may not be entirely
reliable. The age of the twenty-one patients ranged from 30 to 75 years. The
average age was 57 years.

Three of the twenty-one patients showed no evidence of pre-existing disease.
In the remaining eighteen patients there was associated disease which was
diagnostically classified as hypertensive cardiovascular disease in nine patients,
rheumatic heart disease in four, arteriosclerosis in two, thryotoxicosis in one,
coronary atherosclerosis in one, and alcoholism with complicating broncho-
pneumonia in one. In three patients, early congestive heart failure was evident.

Twelve of the twenty-one patients had received no specific therapy. Four
of the entire group had received full doses of digitalis and had received mainte-
nance doses of this drug for a number of weeks before the present study was
undertaken. Three patients had received digitalis and quinidine, and two had
received quinidine alone. None of these nine treated patients had been helped
by the therapy they had received.

Following the intravenous administration of lanatoside .C to the twenty-one
patients under observation, a primary slowing of the ventricular rate occurred
within one hour. In four, the primary slowing of the ventricular rate was lacking.
In one of these four patients, a slow sinus rhythm was established within twenty
minutes. In four of the entire group, sinus rhythm was established without any
medication other than the initial dosage of lanatoside C. The time needed for
this conversion varied from twenty to sixty minutes. Auricular fibrillation was
established after the administration of lanatoside C in fifteen of the group in
from two to seventy-two hours. In one patient auricular flutter continued for
thirteen days before auricular fibrillation was established. In one patient the
flutter was not converted to either auricular fibrillation or sinus rhythm. This
patient suffered from thyrotoxicosis and was eventually treated by surgery.

1 Kc * « iofiKK L'^kopL^smo'jim C \.np Qdinii'Ksk.sih kue i”. the The ktment ok Twenty -On r, P«iemh Wnii Ac!itrrt,ui Ronm Oint'd

Vi

i.

IS’b.

* ^ V:

■•, ; i:i iS"'.K

• • •. • ■■.!.' ..'::!;:':;5>:~!r;3T

I .

Ji.

i;u 2 to 1 A^V thopresencf of associated disease. .4. j

i.'>i-r4ir.p !,r, of i-aa-.t«,ide v «“*'««?• B, Increased A-Y bind: fc

f Afj/r '5,,'' auricular /ibriiiaHon .sev

c 5 - i ■1 'otsj ‘ .sinus rhythm urerity-four iioi

. 4 , Auricular
four hours
.seventy-two
hours after

<■. t",' *■' . «r aiirU-uiar by latmto^ido C nnd nuliiKIltio. A. Auricular

M * ^ »>lock:. _ Venlrinilar rate, i.V) per niinuie. If. Thirty ininutf; artcr I.fi niR. of

Note «lfmliu: effect with incrca«('(l A -V block. C, Conversion to auricular

M-t'.XTli-xs' rnrolc It« nsinf-arancc.

AMERICAN HEART JOURN'AE

f<2s

Ousniciin#.' sulfate wa? giv'cn orally to fifteen of those in whom auricular
utt.-r was ronverted into auricular fibrillation. In addition, a maintenance
.,f lanalo.ride C, consisting of 1 mg. daily, was given. One patient was
to qiiinidirie and the drug had to be discontinued. In the remaining
!; irvn patients of tins group, auricular fibrillation was successfully converted
rliythm over a period of from twelve hours to ten days. The dosage of
ahne was based on individual tolerance and clinical results, and varied from
0 . 1.44 Gm. in twenty-four hours. In one patient the auricular flutter re-
!•<’ iinniediatc!}' after the quinidine was discontinued. This patient had
ao !.!(■ rlieumatic heart disease with a history of multiple attacks of auricular
■irox.winal tncln cardia and auricular flutter since childhood. In another, sinus
I', thru was followed by nodal tachycardia and sudden deatli. ' Autopsy revealed
a- presence of an extensive nu'ocardial infarct involving the interventricular
•otuin and a portion of the interauricular septum.

E.

Tie. 2 (Cont’ti ). — Ear complete legend, see page CZC.

The entire group of patients with successfully restored sinus rhythm re-
ceived a maitUenance dosage of lanatosidc C and were observed for a period of
from two t<i thirty-four months following the institution of this study. The
average time of tihservation was clev'cn months. So far as we have been able to
determint”. there has nru been a single recurrence of auricular flutter. As a rule
the >{wce-‘^funy treated members of this group were discharged from the hospital
within oiui week after the restoration of normal rh^'thm.

TANDpWSKY ET AL. : LANATOSIDE C AND QUINIDINE SULFATE 629

Fig. 3. — Case 2. Direct conversion of auricular flutter to sinus rhythm. Note: Carotid pressure
was ineffectual. Sinus rhythm obtained in 50 minutes following l.G mg. of lanatoside C intravenously.
Tracing taken in Lead II.

DISCUSSION

On the basis of historical and clinical evidence, we feel justified in classifying
the auricular flutter in this group of patients as established. Alany of the patients
had failed to respond to varied therapeutic procedures, including quinidine and
digitalis leaf alone and in combination. After reviewing the literature and
considering our own experience, we feel that quinidine has no place in the initial
therapy of auricular flutter. There are sound pharmacologic reasons for its fail-
ure. Digitalis, on the other hand, may be initially effective in the conversion of
this arrhythmia to sinus rhythm or auricular fibrillation, especially if it be given
intravenously in full dosage as the glycoside lanatoside C. Digitalis leaf fre-
quently fails to convert this arrhythmia, and, when it does, this conversion is
invariably very slow in occurring. Lanatoside C, due to its rapidity of action
and strong vagal effect, has been shown to possess superiority over digitalis leaf
in the treatment of established auricular flutter. This action is further fortified
by follow-up maintenance therapy with the same drug. In patients whose
auricular flutter was successfully converted to auricular fibrillation, the time for
the conversion varied from two to seventy-two hours; in one patient the con-
version did not occur until thirteen days after the initial medication. Serial
electrocardiograms made at frequent intervals during the transition from auricular
flutter to auricular fibrillation were exceedingly valuable therapeutic guides.
We found that adequate medication should be maintained until conversion is
complete. Utmost patience should be combined with careful clinical observation
throughout the conversion period, particularly when complicating disease is
present, as it was in four patients of our series. The presence of associated
disease unquestionably prolonged the conversion period.

Little attention has been given to the primary slowing of the ventricular
rate which occurs when lanatoside C and other forms of digitalis are given in
auricular flutter. This slowing effect designates an increase in A-V block, and

D.

I'ig. 4.^Case 13. Dii'ect conversion of auricular flutter to sinus rhythm with 1.6 mg. of lanatoside
b intravenously. A, Auricular flutter with a ventricular rate of 150 per minute. B, Two hours later
demonstrating slowing effect and increased A-V block. C, Twenty-four hours after lanatoside C estab-
lishment of sinus rhythm. Note: Occasional auricular premature contractions were present. D.
Three days later. Patient receiving 1 mg. lanatoside C daily.

AMKRICAN HEART JOURNAL

?|i.\ f<?'K'k u-ual!v precede? the appearance of auricular fibrillation. We wish
the necessity of continued lanatoside C therapy in maintenance
d> • -.AC until auricular fibrillation makes its appearance.

it !- <iiihcuU to explain the mechanism of the direct conversion of auricular
■. r utt-i a simin rhythm. This occurred in four of our patients. We feel that
- Of! '•ion mipht have occurred spontaneously in due time without the aid
di( .iti'in

! he cfiect of quinidinc in the presence of auricular fibrillation is xvell known;
^ dr tit; is yiven according to individual requirements, satisfactory’^ clinical
a . i tM‘ne=ts can Im* e.xpccted. In this study the time necessary for the conversion
. i .liiricular fibrillation into sinus rhythm by the use of quinidine varied from
• Achc hours to ten days.

When su^lained auricular flutter requires both lanatoside C and quinidine
!!i 'eiiuence to produce sinus rhythm, it seems plausible to assume that the
t i.!!\<TKum would not have occurred spontaneously. The use of these drugs,
thi o fore, appears to be of value in the treatment of auricular flutter.

SU.MMARY AND CONCLUSIONS

1. Lanatoside C and quinidine sulfate used in proper sequence are valuable
drug^- for the corn’cr.sion of established auricular flutter into normal sinus rhj’-thm.

2. Lanatoside C in full digitalizing dosage (1.6 mg.) followed by mainte-
nance dosage (1 to 2 mg. daily) frequently converts auricular flutter to auricular
fibrillation, and less frequently to sinus rhythm.

A. Followang the administration of this drug, a primaiy slowing of the
ventricular rate occurs which, in the main, is due to increased A-V block. This
slowing usually preccde.s the conversion of auricular flutter to auricular fibrilla-
tion.

4. Except in the direct conversion of auricular flutter to sinus rhythm, the
action of lanatoside C can be readily understood.

5. The action of quinidine in the presence of auricular fibrillation is quite
dependable and well known.

6. hollowing the con\'er.sion of auricular flutter to auricular fibrillation by
l.'uiatoside C, the use of quinidine has proved of especial value in this study.

j. C-ont'ersion of established auricular flutter to sinus rhythm can be ac-
compli<hcd in tiie presence of diversified pathologjL

8, Maintenance dosage of lanatoside C has proved of value as prophylactic
therapy folknving the restoration of normal sinus rhythm.

l.

KEFEREXCES ^

'Miire. r, fJ.: Ifrnrt Di-e.-tvi.. fij. A, x,.^v York, 19-J4, The Macmillan Co., p. 907.

Lcv\i:. 1,, D.'un . A- N'., Hir-.ni, C. C.. and Wedd, M.; Obserentions Relating to the
■Ji* Omnidine Upon the Dog’s Ile.nrt; With Special Reference to Its .Action in
Lbnjc.al bibnllation of the .Auricles. Heart 9: 55, 1921.

! V Ij' Cotir-t- and Tre.itmcnt of .Auricular Flutter, Quart.

, TANDQWSKY ET AL. : LANATOSIDE C AND QUINIDINE SULFATE : 633 .

4. Lewis, T., and Drury, A. N.: Revised Views of the Refractory Period, in Relation to Drugs ’

Reputed to Prolong It, and in Relation to Circus Movement, Heart 13: 95, 1926.

5. Wedd, A. ,M.: Notes on the Action of Certain Drugs in Clinical Flutter, Heart 11: 87, 1924.

6. Wilson, F. N., and Wishart, S. W.: The Effect of the Intravenous Administration of Digi-;. -

talis in Paroxvsmal Tachj^cardia of Supraventricular Origin, Am. Heart J. 5: 549,
1930.

7. Tahdowsky, R. M.: An Electrocardiographic and Clinical Studv of Lanatoside C, Am.

He.\rt J.24:472, 1942.

8. Lewis, T., Drury, A. N., and Iliescu, C. C.: Some Observations Upon Atropine and Strd- -

phanthin, Heart 9: 21, 1921.

9. Barker, P. S., Wilson, F. N., and Johnston, F. D.: The Mechanism of Auricular Paroxysmal

Tachycardia, Am. Heart J. 26: 435, 1943.

10. Author’s obsersmtions during the past five years.

11. Ray T., and LaDue, J. S.: The Intravenous Administration of Lanatoside C to Patients

Taking Maintenance Doses of Folia Digitalis Up to the Date of Hospitalization With '
Recurrent Congestive Heart Failure, Am. Heart J. 30: 335, 1945.

12. Tandowsky, R. M., .Anderson, N., and Vandeventer, J. K.: -An Electrocardiographic and

Clinical Stud\’ of Various So-Called Cardiac Drugs, Am. Heart J. 28: 298, 1944.

13. Tandowsky, R. M.: Prophjdactic Use of Lanatoside C in Auricular Paro.xysmal .Arrhy-

thmias. Am. Heart J. 29: 71, 1945.

MLfXTROCARDIOGRAPHIC CHANGES OCCURRING DURING
TREATMENT WITH FUADIN SOLUTION

S. B. Bkasrr, M.D.X and R. Rodriguez-Molina, M.D.f

^ '^IJXICAL nu’dicine recognizes heart disease as one of the commonest causes
for sudden death. In any condition, therefore, in which sudden death
o!curs, a cardiac origin should be suspected; moreover, evidence for unsuspected
(Aidjac dysfunction in nonfatal cases of that disorder should be sought for.
< 'in- such disorder is the toxicity due to antimony therap}’’ of schistosomiasis.
M.mi/er and Krause,’ after observing such a fatality, performed electrocardio-
iji.ims routinely on twelve patients receiving intravenous tartar emetic and found
il'.'nrmalitk's in eight of them, all of whom were asymptomatic. The accidental
iuHiing of similar electrocardiographic changes in a patient receiving the reputedly
ic'S toxic fuadin (sodium antimonjj- pyrocatechin) led to the present sj'stematic
electrocardiographic study of twenty-five patients under treatment for schisto-
^oIniasis with that drug.

PLAN OF STUDY

All twenty-five patients were Puerto Rican soldiers vith schistosomiasis
(.Mansoni) who were receiving a uniform course of fuadin therapy. Electro-
cardiogranisj were taken before and during treatment (Table I). The usual
limb leads and CF 4 were taken with the patient in the same position and with
.standardizations recorded no sooner than two and one-half hours after meals''
and one hour after the fuadin injections. Additional electrocardiograms were
taken just after the tenth injection on certain positive cases as follows: two in
inspinition and expiration both in the recumbent and upright positions; one
fifteen minutes after the intravenous injection of 1/50 gr. of atropine dissolved in
10 c.c. of distilled water; one with bilateral carotid sinus pressure. In fourteen
of the twenty patients who showed electrocardiographic changes, twenty-two
follow-up electrocardiograms were performed during the three weeks after cessa-
tion of therapy.

The tracings were analyzed for all the conmion factors. The P-R interval
was used as the basis for the isoelectric line and five successive complexes were
averaged for each measurement. Following the criteria of Larsen and co-
v.-orkers.'‘ the outer limit of normal variation of the amplitude of T waves was con-

flfC'ivfU for i>ul)I[cat!on 20, UUfi

*A*a«{Mii IR XttUirinc. nar\anl Mwlical School, and Head of Tho Diahctic Clinic, lioth Tsi-arl
Ronton, <on IcaNc of ah'.faco In the Unln'l States Army).

I.lsa.fitan! l*r!>rc<;-or of Trojdcal .Mt^ncinc, School of Tropical .Medicine. San .Tuan. Puerto Rico,
ColumbSt tnUersitj, Nc^ York. N. Y', Ion Icraso of nhsenco in the United SIatf« Ann> )
tT!-e<5«RiTan;{ectric t;!rctn>C3rtHo;:r.'»ph {Model U) was used tliroii!;liout.

Ottl

r

BEASER AND RODRIGUEZ-MOLINA :

ECG CHANGES AND FUADIN SOLUTION

635

Table,!. Fuadin* Therapy (Dosage Schedule)

Day of treatment

1

0

1 t

1

1

2 1

. .„|

3

5

7

9

11

13

15

17

Number of fuadin injec-
tions

0

i '1 1

2

■

4

5

6

■

8

9

10

Dose of fuadin in cubic
■ centimeters ,

0

1.5

3.5

5

5

5

1

5

1

5

1

5 ^

5

5

Accumulated dose of fua-
, din

In cubic centimeters

In milligrams

0

i

1.5

5

10

15

1

j

20

1

25

!

30

j

35

40 j

45

0

0.63

1.89

2.84

Accumulated dose of
antimony in milli-
grams

0

1

0.085

1

1

0.255

0.383

ECG performed

Control

ECG

*

ECG

ECG

ECG

*Each cubic centimeter of fuadin solution contains 0.063 Gm. of fuadin and 0.0085 mg. of trivalent
antimony.

sidered to be 0.1 mv, and definite changes had to persist for at least ttvo tracings
in order to be regarded as significant. Certain cases were considered to show no
change, even though the T waves had a definite tendency to decrease in voltage
(six in all), since they did not conform to the foregoing criteria. The ventricular
gradient was measured* in one instance (Leads 1 and II of A and D of Fig. 2)
according to the method of Wilson and co-workers.'’

RESULTS

Significant changes from the normal were noted only in the T waves and S-T
segments (Table II and Figs. 1-6). The analysis which included all important
elements of the tracings showed no significant QRS, Q-T, or rate changes. Of
the total of twenty-five patients, twenty, or 80 per cent, showed significant
", decrease in the height of the T waves in two or more leads. The amplitude of the
T waves decreased therefore in fifty-nine of a total of 100 T waves. Seven
patients developed T-wave changes in all four leads. In two (Figs. 2 and 4),
T4 had a cove-plane configuration.*® The regression of the abnormal changes of
forty-one T waves in fourteen patients was studied in detail in terms of the per-
centile return toward the pretreatment normal value of each T wave in the
three weeks following cessation of treatment (Table III). These values can be
considered only as estimates of the speed of recovery. Changes in position,
inspiratioii and expiration, atropine, and carotid sinus pressure did not signifi-
cantly alter the T-wave changes noted previously. The ventricular gradient
, showed a counterclockwise rotation to the left and a decrease in magnitude
(Table IV and Fig. 7).

*We are indebted to Dr. A. Stone Freedberg for this analysis.

FIs. l."-CaHo 1. ,1, Control: li and C. Injections 7 and 10. resiioctlvcly ; T) and /J, four and eleven days, re.spccllvely, after C.

^\MKKirAN HKART JOURXAT.

. 1 .

( it”. ;! —

TAtu.n II.

/{.

c.

D.

0, .i. I’ontfol; and C. Injcciions 7 and 10. rost’t^tSvoIy ; D, three days after C.

Analysis ok thi; 'I'-W.avf. Cuaxchs Occurring During Ft;Ai)iN Therapy

i

!

1

; N I'M HER or PATIENT.s -
m'.vni.oriNG t-wave

1 changes

NUMHKR OF PATIENTS
DEVEl.OPING T-\VAVE
CHANGES AT INJECTION
NUMHER

NUMHER OF P.VTIENTS WITH
MAXIMU.M change AT
INJECTION NliMRER

'i

'

f

;

1

7

10

10

T:

■' 1-5

6

r~:

1

2

1!

Ti

: It)

14

.

0

0

-

17

i

R

; 5

4

3

1

2

S

1\

; IS

i 14

>

-

2

12

\'n;.tlKr

.'9

i

\ 55

8

4

10

45

P.'f ct ni

tm

;

*•

i

1

17

76

AMEKiCAK HEART JOURNAL

L l\ . Ml \*rKr.’

■,u:nt or Vf.ntriculak

Gradient of Case 5 (Fig. 2)

! ■.non

CONTROi. (a)

AFTER rCADIX (d)

-1-34.0 111. V. s.

-P23.5 m. V. s.

T,

-1-59.0 m. V. s.

-f 16.0 m. V. s.

-rl7.0 m. V. s.

-f-16. 0 ni. V. s.

r.

-4-31 .0 ni. V. s.

— 28.0 ni. V. s.

t “

*

35.5 m. V. s.

24.0 ill. V. s.

-r

-f 13“

M

59.0 ni. V. s.

46.0 m. Y. s.

+ 1°

-68“

.•‘Ui'WT

95.0 m. V. s.

54 m. V. s.

0”

-44“

DISCUSSION

Aiuinuiny has been shown to have no immediate effect upon the electro-
< iu!u>;;ram of the dog'-' but does cause weakening of the heartbeat with cardiac
.hi. nation both in dogs'" and frogs. In more prolonged toxicity experiments
m dogs, 111 !.“: drug has been shown to accumulate chemically much less in the heart
titan in the lungs, Ii^'er, and kidneys.'-'’’ Likewise, pathologic changes in the
li\cr ,in(i kidneys preceded heart involvement in the dog. Severe symptoms
of hep.itic and renal damage -were evident at a time when the contrastingly mild
hf-ari dain.age was clinically not evident (electrocardiograms were not taken in
the>(‘ e.x peri men is).

In man, the toxic symptoms after antimony treatment consist of vomiting,
u'li.ipse, fever, and muscular pains. These occur in only 1 per cent of patients
leeeiving fuadin (le.'^s than after tartar emetic). The reasons for the variation in
individual susceptibility are unknown, but the excretion of fuadin has been
noted to vary from person to person, with a noticeable delay in those with renal
excretory difhculty. Alainzcr and Krause,' in their electrocardiographic study
of palieni,« under tartar emetic therapy, noted that the heart rate decreased
slightly,” that the T waves became flat or inverted, and that the S-T and T
elctnents became ‘‘indistinctly separated and fused with one another.” The)'
found that the changes occurred early (usually in the second tracing) after 0.72
to l.OS Gsn. of tartar emetic, but they did not determine the recovery rate b}'
following their cases. Magalhaes and Dias” found similar T-wave changes in
iwenty-one patient* receiving anlimon}' therapy. These changes were present
in seven of fourteen of their recorded electrocardiograms. Of these, one-half
til!' pAtient.s had received tartar emetic, but it was not clear which antimony
compound* the renmining patients had received. After completion of thc.se
studii's. Tarr’*^ published a preliminary report showing that tweh'e of thirty-eight
patients receiving intravenous tartar emetic and two of twenty-eight patients
receiving inlrantuscuiar fuadin showed significant electrocardiographic changes
ronsisTing of flerri-.ipc in the voltage of the T waves.

* i I ^ rCfTvU" Tr,«. n to bf' vttKUs

AMERICAX HEART JOURNAL

.1. Tl. ■ - C. D.

flsi. 25. A. Coiurol; B nnd C, injections 3 and 10. respectively: D. .seven days after C.

The ntechanisni of the fuadin effect is unknown, but it seems to be definitely
reversible. Digitalis, which also has a reversible action upon the myocardium,
affects chiefly the magnitude of the ventricular gradient (decrease). A shift in
direction of the ventricular gradient has also been noted in myoairdial ischemia.’'
This is of interest since Magalhnes and Dias’^ ascribed the effects of antimony
"to dilatation of the capillaries or the coronary circulation with diminution in
the effective circulation to the heart,"

Of more than ihtx^retica! interest is the similarity of the change.s seen after
.administration of fuadin and those ob.served in patients with intercurrent in-
fection’’' or phosphorus poisoning'-* who have been shown to develop similar un-
siuperSt-d and asym[Uomatic T-wavc changes and who may die suddenly with
pathulogicalh- demon.stnited myocardial changes. Practically, (he fact.s warrant

BEASER.AND RODRIGUEZ-MpLINA: ECG' CHANGES AND FUADIN SOLUTION 643

the clinical precaution that the frequentty repeated courses of fuadin be spaced
four or more weeks apart to avoid a cumulative effect upon the myocardium,
even though that effect is probably reversible in nature.

SUMMARY

,1. Of twenty-five patients receiving a course of fuadin therapy for schisto-
somiasis, twenty showed decrease in voltage of the T waves of the electrocar-
diogram.

2. These changes occurred early (60 per cent after the third injection)
and were reversible, regressing in three or more weeks.

. 3. The ventricular gradient in one patient was analyzed and showed a

, definite shift in direction.

/ REFERENCES

' ■ 1. ' Mainzer, F., and Krause, M.: Changes of the Electrocardiogram Appearing During Anti-

monj' Treatment, Tr. Roy. Soc. Trop. Med. & Hyg. 33; 405, 1940.

2. Khalil, M. B.; The Specific Treatment of Human Schistosomiasis (Bilharziasis) With Spe-
cial Reference to its Application on a Large Scale, Arch.'f. Schiffs- u. Tropen-Hyg.
T , ' V 35:1,1931.

3; . Khalil, M. B.; Individual Variation in the Excretion of Drugs as an Important Factor in
: '■ Their Therapeutic Results. A Practical Method for Detecting the Schistosomiasis

' - • . Cases With So-Called Idiosyncrasy to Antimony to Avoid Fatalities and Complica-

. . ; , tion, J. Egyptian M. A. 19: 285, 1936.

' 4; Gardberg, M., and Olsen, J.: Electrocardiographic Changes Induced bj' the Taking of

. - ... Food, All, Heart J. 17 ; 725, 1939.

5. ' Larsen,: K., Neukirch, F., and Nielson, _N. A.: Electrocardiographic Changes in Normal
Adults Following Digitalis Administration, All. Heart J. 13: 163, 1937.

644

AMERICAN HEART JOURNAL

6. Wilfon, F. X., ^lacLeod, A. G., Barker, P. S., and Johnston, F. D.: The Determination

and the Sitinificance of the Areas of the Ventricular Deflections of the Eleclrocardio-
prani, Am. Hiakt J. 10; 46, 1934.

7, Rothschild, M. .\., Mann, H., and Oppenheimer, B. S.: Successive Changes in the Electro-

cardiogram Following .401110 Coronarv .Arterv Occlusion, Proc. Soc. Exper. Biol. &
Med. 23; 253, 1926.

S. Meira, J. and Kamos, J., Jr.: Consideragoes sobre o elcctrocardigrama na esquisto-
soiniase mansoni, Hospital, Rio dc Janeiro 26: 77, 1944.

9. ChristOfJoss, J. D., Rajamanikam, X., and Krishnaswam;-, R.: Some Observations on the
Cardiovascular Action of Urea-Stibaminc, Indian J. M. Research 21: 617, 1934.

10. Kato, K.: Ueber die pharmakologischen Wirkung von .A-ntimon III-bis-Brenzcatcchindi-

sulfonsaurem Xairium (Fuadin) und Xatrium Antimon Ill-bis-Prolocatechusaurcm.
(IL Mitteilung) Wirkung auf die Herzaktion, Blutgefasse und den Skelettmuskel,
Okaynma-lgakkai-Zasshi .50; 1867, 1938.

11. Voshinuira, S.: Ueber die Digiialiswirkung auf das tinrch einige Antimonverbindungen

geschadigte Herz, Jap. J. M. Sc., IV, Pharmacol. 12; 185, 1940.

12. Hassan, A.: The Distribution of Antimony in the Body Organs Following the .Administra-

tion of Thernpeutic .Antimony, J. Egyptian M. A. 21: 123, 1938.

13. Boyd, T, C., Xapier, U. E., and Roy, A. C.: The Distribution of Antimony in the Body

Organ.s, Indian J. M, Research 19: 285, 1931.

14. Fninz, G.: Zur pathologischen Anatomic der Antimonvergiftung, Arch. f. exper. Path. u.

Pharmakol. 186; 661, 1937.

15. Mapalhrie.s, B. F., and Dias, C. B.: Esquistossomosc dc Manson-Estudos, Mem. Inst.

Oswaldo Cruz 41 ; 363, 1944.

16. Tnrr, L.: Effect of the Antimony Compound.s, Fuadin and Tartar Emetic, on the Electro-

cardiogram. .A Preliminary Report, Bull. U. S. Army M. Dept. 3: 336, 1946.

17. B.ayley, R. H., and Monte, L. A.: Acute, Local, Ventricular Ischemia, or Impending

Infarction, Caused bv Dissecting Aneurj'sm. Case Report With Necropsv, .Am.
Ih;.\KTj. 2:>; 262, 1913.

18. Candcl, S., and Whcclock, M. C.: .Acute Non-Specific Myocarditis, .Ann. Int. Med. 23;

. 109 , 1945 .

19. Xewburger, R. -A., Beaser, .S. B., and Slnvachman, H.: .A Case of Phosphorus Poisoning

\Mth Recovety Accompanied by Electrocardiographic Changes. To be published.

ORTHOSTATIC PAROXYSMAL VENTRICULAR TACHYCARDIA

Captain Michael Peters, M.C. and Captain Sidney L. Penner, M.C.

Army of the United States

TN THE course of observations on the effect of changes in posture and various
drugs on the cardiovascular system, we encountered an instance of orthostatic
paroxysmal ventricular tachycardia. We believe this finding is unusual enough
to warrant reporting.

report of case

Mrs. H. H., aged 24 years, was first seen in June, 1945, complaining of attacks of rapid heart .
action occurring since January, 1944. Each of these attacks began with a sensation of "pressure,
against the heart and gas in- the stomach.” The heart would then begin to beat rapidly, stop
for a few beats, and then beat fast again. This was accompanied by a stuffy feeling in the ears
and a sensation of blood rushing to the head. However, the attacks never occurred while the
patient was lying down but appeared only in the upright position, and in this position were pre- '
cipitated by excitement or mild exertion. From January, 1944, to June, 1944, attacks of rapid
heart action occurred about once a month. In June, 1944, she became pregnant. The attacks
were unchanged for the first five months of pregnancy, but did not recur during' the remainder
of the pregnancy nor during a rather difficult three-day labor. However, two weeks after de-
liver}'-, she had an identical episode on getting out of bed for the first time and since then the
attacks have occurred once or twice weekly. In the free intervals she has enjoyed excellent health
except for "some nervousness.” She has never had any dyspnea or edema. Past history in-
cluded measles, mumps, chicken pox, and whooping cough in early childhood without known
sequelae. There was no histoyv of diptheria, .scarlet fever, or rheumatic fever in any of its varied ,
manifestations. She did not use alcohol, coffee, tobacco, or any medication.

The physical examination was entirely normal. The blood pressure was 1 10/60. The blood ;
count, urinalysis, and blood Kahn were normal. The basal metabolic rate was —4 per cent.
X-ray e.xamination of the heart in the posteroanterior and left lateral positions with barium in the
esophagus was normal. The lung fields were clear.

■■ Two weeks after the original consultation, the patient \vas seen during a spontaneous attack
of tachycardia. At this time the apex and pulse rates were 150 to 180 per minute and were
irregular. There were runs of rapid regular rhythm interrupted frequently by a slower rhythm.
She was apprehensive and tremulous but not in acute distress.

An electrocardiogram was taken in the supine position. Leads I, II, III, and CFo showed,
brief runs of ventricular tachj'cardia, interrupted by one or two sinus beats. Lead CF 4 showed a
normal sinus rhythm. . This change to regular rhythm did not surprise the patient, who pointed
but that she could always stop an attack by lying down but that the tachycardia would recur
.upon resuming -the upright position. An electrocardiogram was therefore taken in the upright'
position; this record showed ventricular tach 5 'cardia once again.

On July 1, 1945, the patient stated that she had had three attacks in the preceding two.
weeks. E.xamination showed a regular sinus rhythm. After fifteen hops on each foot, she de-
veloped an attack of ventricular tach 3 '’cardia proved by an electrocardiogram. Ergotamine

Received for publication Oct. 29, 1945. •

645

AMKKICAN- HEART JOURNAl.

sa't!'..!-' i' hk; . qjvi'n intravenously while the patient was in the standing position. She
I. ' nn -i o! ii-r-ting weak .tnd sat down. An electrocardiogram in this position still showed
•, nfn -ihr t,>< htx.'trdi.i, hut twenty-five minutes later the electrocardiogram showed normal
^ .Mjt :!■•, -Inn When •'ho sttxtd up. the tachycardia did not recur, and the ne.Kt day she reported
.. -<•! iirri iiu' of the attack''. She was then advised to take 0.3 Gin. of quinidine sulfate daily.

I jo^ iniS, ''he reported, by phone, that she had not had any further attacks. Unfortu-
. ' !' '!;f w,'!*' lo'i to our further observation after this date.

DISCUSSION

Tlie diagnosis of ventricular tachycardia depends prtinarily on electro-
rardic'goipliic rinding.s aithough it can be suspected clinically. It has been
•'h/n.vn' lha! the rhythm is not absolutely regular. Minor variations in the length
of the cardiac cycle occur which can be detected bj' careful auscultation. In
.iddiiion, there are variations in the inlensiU'^ of the first heart sounds which are
flut- lo the changing time relations between auricular and ventricular systole.
( ob.servalion may also reveal a waves in the jugular pulse which are slower
in rate than the ape.x beat. Further, vagal stimulation does not influence the
heart rate in ventricular tachycardia as it does in paro.vysmal auricular tachy-
cardia and in auricular flutter. If auricular fibrillation is known to have existed,
the sudden development of a marked rise and fall in the apex rate would suggest
ventricular tachycardia, espccialljr after heavy digitalization,-

Although ventricular tachycardia had been recognized as early as 1909,^
the rriten'a for the electrocardiographic diagnosis were first cyrslallized by
Robinson and Merrmann in 192I.‘‘ As amended by Cooke and White,* they
include:

1 . The irkntifiralion of P waves (iuring the paroxysm at a slower rate tlian the
QRS complc.xes,

2. A paroxysm of abnormal ventricular complexes, i. e., three or more at a
rapid r.tte, occurring during auricular fibrillation.

.3. T!ie on«ei of tachycardia witli an abnormal ventricular complex.

•1. A clo.-=e resemblance, in the same lead, of the QRS complc.xc.'' of the ven-
tricular premature beats to the QRS complexes occurring tinring the tachy-
cardia.

Only one of (he.se conditions is needed to establish the diagnosis of par-
oxy.^mal ventricular tachycardia. The prc.sent ctise illustrates 3 and 4 of the
criteria just given (Figs. 1 and 2). We were unable to identify P waves during
the paroxtkm.

OtniceJ /'Vo.'amr.— "Ventricular tachycardia is not a common arrhythmia.
C ooke and White- found the disturbance only twenty-four times in a study of the
records of 25,000 patients. Most articles on this subject report isolated cases;
the largest personal scries comprised thiriy^-six c^ises,^ while Cooke and White
rejK'rted twenty-seven

Ikiroxysma! ventririilar tachycardia is u.sually due to serious organic heart
d;-ease, <-5pirrially coronary artery disease, but may de%'e!op after the administra-

PETERS AND PENNER: ORTHOSTATIC PAROXYSMAL VENTRICULAR TACHYCARDIA 647

tion of digitalis,® epinephrine,^*® or related drugs.® It may also be induced in'.
presumably normal hearts by chloroform*® and similar compounds.** In addi- .
tion, a limited number of instances of paroxysmal ventricular tachycardia has
been reported in relatively young persons with normal hearts and no external
precipitating causes.®* ®* *®"*® Follow-up on some of these patients was continued
for as long as fourteen years without developing any signs of heart disease.

648

AMERICAN HEART JOURNAL

I

The symptoms associated with ventricular tachycardia ^'ary considerably,
depending on the heart rate, the duration of the paroxysm, the degree and
type of heart disease present, as well as the coexistence of extracardiac pathologic
states. Although some subjects have no symptoms and may be unaware of the

rU*, e, — \i( fit-cimcardfoisrani made wUli !!ii- patient erect .shows runs of vcitricular paro\ysninl tacliy-

eardia iiiterriip'etl by a few uonnai cycles.

arrhythmia, most patients complain of palpitation, precordial fluttering, or weak-
nc.'S. In some in.stance.s the rapid heart rate may be associated with a diminisiied
cardiac output'^'-'* re.^ulting in dizzine.ss and .syncope." When the ventric-
uiar rate is rapid and the paroxysm prolonged, heart failure maj' result, even in
the ab'^ence of organic heart disease.^ Anginal pain may be a conspicuous
featitre in patieiu.s with myocardial damage, though this need not be present.-'

PETERS AND FENNER ; ORTHOSTATIC PAROXYSMAL VENTRICULAR TACHYCARDIA 649

In many cases, such as the one presented here, ps 3 'chogenic symptoms occur as
a result of repeated attacks over a long period of time in an emotionally unstable
individual.

The individual paroxysm of ventricular tachycardia usually begins with
isolated ventricular premature beats, followed by short runs, which finall}^ become
continuous and replace the normal sinus rhythm. The physical findings during
the paroxysm which would suggest to the clinician the nature of the arrhythmia
have already been outlined, as have the electrocardiographic criteria.

The prognosis of ventricular tach37cardia is properly regarded as ominous,
due both to th9 arrhythmia itself and to the almost invariably' co-existent heart
disease. In a group of twenty’^-two patients with paroxy^smal ventricular tachy-
cardia and coexisting heart disease, twenty died within two years of the first
attack.^ Of fifty’’ similar cases reported by Strauss,-^ forty died within six months
of, the onset, with an average duration of life of twenty’^-four days. However,
the prognosis may’’ be regarded as more favorable in patients with chronic heart
disease, in the absence of acute cardiac damage,-^ or when appropriate therapy’ is
employ’ed early’ in the course of the paroxy’sm with a favorable response.*®'-®

In apparent contrast to this larger group of patients with organic heart
disease is the limited group in whom no heart disease can be demonstrated on
examination; this group appears to have a far more favorable prognosis. Cooke
and White^ have continued follow-up on such cases for as long as nine, twelve,
and even fourteen y'^ears after the onset of paroxysms of ventricular tachy’cardia.
However, even in this type of patient the arrhythmia carries hazards of its own,
for there always remains the possibility of sudden death due, perhaps, to the
development of ventricular fibrillation. Such cases have been repeatedly’’
reported. Further, the development of severe® or even fatal heart failure
as the result of an uncontrollable attack has been recorded. With the more wide-
spread use of appropriate therapy’, including parenteral quinidine in adequate
dosage,29 particular hazard may, at times', be averted. Specific criteria
for a group of “benign” cases of paroxysmal ventricular tachy’cardia have been
suggested.^® They are (1) the youth of the patient; (2) the long follow-up;
(3) clinically normal hearts; (4) normal electrocardiograms during regular sinus
rhythm ; and (5) nomorphism of the aberrant QRS complexes during the tachy’-
cardia; However, in view of the hazard inherent in this arrhythmia, it is believed
that the appellation of “benign” is inappropriate.

Physiologic Considerations . — It has long been known that sy’mpathetic stimuli
can cause ventricular tachy’cardia. Hoff and Nahum®® were able to produce’
ventricular rhythms by’ administering adrenalin and, conversely’, found that
benzol poisoning, which regularly produced ventricular tachycardia, was in-
efectual in the absence of the adrenal glands. Kirk and Kilpatrick'^ reported a
patient with coronary artery’ occlusion in whom adrenalin produced ventricular
tachycardia, while Herrmann® reported a similar experience with ephedrine.
Furthermore, mecholy’l, a parasympathomimetic drug, was found to abolish the
arrhythmia in animals,®® while atropine, a parasympatholytic drug, induced a
paroxysm in Scott’s patient.®

650

AMERICVN HEART JOURNAL

Ii is also recognized lhat the sympathetic nervous system plays an imporlant
part in the vascular adjuslmenls taking place in man on assuming the upright
position. The inlilial transient drop in blood pressure of 5 to 40 mm. Hg
stimulates receptors in the carotid sinus, aortic arch, mesentery, and perhaps
elsewhere to raise the pulse rate and bring about x'asoconstriction in both the
splanchnic and peripheral areas.'* These compensatory mechanisms are mediated
l)y the sympathetic nervous system. In some individuals, the adjustments are
inadequate and result in orthostatic h 3 ’potension,**- while in others, evidences of
oxessive stmipathetic aclivitj' can be found. Thus, Wendkos'*® has reported
T-wave changes in the elect rocjtrdiogram which appear on assuming the upright
position and enn be abolished b\’ administering a sympatholjnic drug. Com-
parable postural effects on the P-R interval have also been noted.*'®’'*®

in the present case there was a clear-cut relation of the parox^'sms of ven-
tricular taclnx'ardia to posture, noted both in the historj' and on clinical observa-
tion. .A^ltacks occurred only in the upright position. They could alwa^'s be
terminated b\' lying down, onR- to recur upon reassuming the upright position.
Further, tlie attacks could be readih’ precipitated bt' e.vertion or e.xciiement,
factors which are known to be a.ssociated with increased sympathetic tone.®’
In several case reports of “benign” ventricular tachycardia, one finds notations
that the attacks were precipitated by e.xert ion, while in one of these cases**
it was noted that the paroxysms were occasional!}^ relieved by the supine position,
resembling our case in this respect. A similar e.xperlence in two cases of auricular
taciiycardia has been reported.®* It is interesting to note that our patient had
no attacks in the last trimester of pregnancy, at a time when increased intra-
abdominal pressure and increased blood volume would tend to minimize the
rellexos ordinarily active on assuming the upright position.

1'hcse considerations, therefore, made it apjicar likely to us that the attacks
of paroxx'smal ventricular lacht'cardia were due to unusualh^ strong sympathetic
tone produced In' assuming the upright position, by e.xerlion, or by excitement.
With this thought in view, the patient was given an intravenous injection of 0.5
mg. of ergotamine tartrate during a paroxysm. Within twenty-five minutes the
attack ceased and could not be reporcluced thirty minutes later by the assumption
of the upright position. Since the pharmacologic action of ergotamine in this
dosage is sx’mpatholytic,®® the result obtained would support the view that auto-
nomic imbalance is the cause of the tachycardia. Unfortunately, we did not have
an opportunity to tr\' mecholyl which was used in animals by Hoff and Nahum.®”
Fertinem to this problem is Scott's observation that atropine, a parasympatholytic
drug, induced a paro.xysm of ventricular tachycardia in his patient. Had a
parasympathomimetic drug Ixen u.sed effect ivelj'- in our case, the role of the auto-
nomic nervous system in the causation of this arrhythmia related to posture
wnuki liavc been strengthened. The fact that mecholyl was used unsuccess-
fuliy in the unusual rase recentb' reported by Chapman®” does not invalidate these
torichi‘'jnn''.

PETERS AND FENNER : ORTHOSTATIC PAROXYSMAL VENTRICULAR TACHYCARDIA 651

SUMMARY

An unusual instance of orthostatic paroxysmal ventricular tachycardia in
a ^'^oung woman with no other evidence of heart disease is reported. The rela-
tion to autonomic imbalance is discussed.

REFERENCES

1. Levine, S. A., and Strong, G. F.: Irregularity of Ventricular Rate in Paroxysmal Ventricular

Tachycardia, Heart 10: 125, 1923.

2. Cooke, W. T., and White, P. D.': Paroxysmal Ventricular Tachycardia, Brit. Heart I. 5;

33, 1943.

3. Lewis, Thomas: The Mechanism of the Heart Beat, London, 1911, Shaw & Sons, Ltd.

4: Robinson, G. C., and Herrmann, G. R.: Paroxysmal Tachycardia of Ventricular Origin
and Its Relation to Coronary Occlusion, Heart 8: 59, 1921.

5. Williams, Conger, and Ellis, Lawrence B.: Ventricular Tachycardia; an Anab'sis of 36

Cases, Arch. Int. Med. 71: 137, 1943.

6. Marvin, H. M.: Paroxysmal Ventricular Tachycardia With Alternating Complexes Due

to Digitalis Intoxication, Am. Heart J. 4:-21, 1928.

7. Kirk, Robert C., and Kilpatrick, E. M.: Ventricular Tachycardia From Adrenalin and

Sinus Standstill From Intravenous Quinidine in Case of Coronar}' Occlusion, Ohio
„ State M. J. 37: 437, 1941.

8. Scott, R. W.: Observations on a Case of Ventricular Tachycardia With Retrograde Con-

duction, Heart 9: 297, 1922.

9. Herrmann, George R.: Disturbance of the Heart Beat, in Stroud’s Diagnosis and Treat-

ment of Cardiovascular Disease, Philadelphia, 1945, F. A. Davis Compan 3 ^

10. Hill, I. G. W.: Cardiac Irregularities During Chloroform Anaesthesia, Lancet 1: 1139,

1932.

11. Geiger, Arthur J.: Cardiac Dysrhythmia and Syncope, J. A. M. A. 123: 141, 1943.

12. McMillan, Thomas M., and Bellett, Samuel: Ventricular Paroxysmal Tachycardia:

Report of a Case in a Pregnant Girl of 16 Years With an Apparently Normal Heart,
Am. Heart J, 7: 70, 1931.

13. Routier, D.: Benign Ventricular Extrasystole With Paroxysmal Tachycardia, Arch. d.

mal du coeur 30: 224, 1937.

14. Anderson, Maine C.: Paroxysmal Ventricular Tachycardia, Am. J. M. Sc. 181: 309, 1931.

15. Routier, Daniel, and Puddu, Vittorio: Benign Ventricular Extrasystole With Paroxj^smal

Tachycardia; 2 Clinical Cases, Arch. d. mal. du coeur 29: 676, 1936.

16. Cassinis, Ugo, and Sibilia, Daniele: Benign Juvenile Ventricular Tachycardia, Cuore e

circolaz. 23: 148, 1941.

17. Bramwell, C., and King, J, T.: Principles and Practice of Cardiology, London, 1942,

Oxford University Press.

18. -Marra, Alfred F.: Report of a Case of Paroxysmal Ventricular Tachycardia, With No

Demonstrable Organic Heart Disease, Which Produced Attacks of Syncope, Am.
Heart J. 28: 810, 1944.

19.. Wiggers, Carl J.: Physiology in Health and Disease, ed. 2, Philadelphia, 1937, Lea &

Febiger;

20. Stewart, H. J., Deitrick, j. E., Crane, N. F., and Thompson, W. P.: Studies of the Circula-

, , , tion in the Presence of Abnormal Cardiac Rhvthms, J. Clin. Investigation 17: 449,

. ■ 1938.

21. Wolff, Louis: The Cardinal Manifestations of Paroxysmal Tachycardias. I. Anginal

Pain, New England Ji Med. 232; 491, 1945.

22.. Wolff, Louis: .The Cardinal Manifestations of Paroxj'smal Tachycardias. II. Vascular

Collapse, New England J. Med. 232: 527, 1945.

23. Strauss, Maurice B.: Paroxysmal Ventricular Tachycardia, Am. J. M. .Sc. 179; 337, 1930.

24. Riseman, Joseph E. F., and Linenthal, Harrj'-: Paroxysmal Ventricular Tachycardia, Am.

■ , Heart J. 22; 219, 1941.

25. Dubbs, Alfred W., and Parmet, David H.: Ventricular Tachycardia Stopped on the 21st
Day b\^ Giving Quinidine Sulfate Intravenously, Am. Heart J. 24; 272, 1942.

65?

AMERICAN HEART JOURNAL

/. \h M'D in, R. L.: \'entricular Tachvcartlia as a Therapeutic Problem in Coronarj- Throm-
hu-is. South. M. J. 36: SOO, 1943.

" \\ii .j't. F. H., Wi^hart, S. W.. MacLeod, A. G., and Barker, P. S.: A Clinical Type of
Paroxy.sinal Tachycardia of Ventricular Origin in Which Paroxysms Are Induced by
Exertion, .Am. Heart J. f?: 155, 1932.

('.mipbe!!, M., and Elliott, G. A.; Paroxysmal Tachycardia; .Aetiology and Prognosis of
100 Cases, Brit. Heart J. 1: 123, 1939.

■> Reich, Nathaniel E.: Sucres-ful Use of a Massive Dose of Qiiinidine in a Case of Intractable
Ventricular Tachycardia, Am. He.xrt J. 20: 256, 1944.

■ ' Hofi, H. E., and Nahum, Louis H.: The Role of Adrenalin in the Production of Ventricular
Rhythms and Their Suppression by .Acet\’l-B-Mcthyl-Choline Chloride, J. Pharmacol.
& Exper. Thcrap. 52: 235, 1934.

’ !. .Xbram^on, David I.: Vascular Responses in the Extremities of Man in Health and Disease,
Chicago, 1944, University of Chicago Press.

.U. Bradbur}' S., and Eggleston, C.: Postural Hypotension, Am. He.vrt J. 1: 73, 1925.

.31, Goodman, L., and Gilman, .A.: The Pharmacologic Basis of Therapeutics, New York,
1941, The Macmillan Co.

31. Miller. Ralph, and Pcrclman, Julius S.: Chronic -Auricular Tachycardia With Unusual
Response to Change in Posture, .Am. Heart J, 29: 555, 1945.

.15. .\le.\ander, H. L., and Baucrlein, T. C.: Influence of Posture on Partial Heart-Block,
Am. Heart]. 11: 223, 1936.

36. .Manning, G. W,, and Stewart, C. B.: .Alteration in P-R Interval .Associated With Change

in Posture, Am. Heart J. 30: 109, 1945.

37. Weiss, Soma: The Interaction Between Emotional States and the Cardiovascular System

in Health and in Disease, Contributions to the Medical Sciences in Honor of Dr.
Einannel Lihinan by His Pupils, Friends, and Colleagues, New A'ork, 1932, Inter-
national Press, Vol. 3, p. 1 181.

38. Wendkos, Martin H,: The Infincnce of Autonomic Imbalance on the Human Electrocardio-

gram, Am. Heart J. 23: 549. 1944.

39. Chapman, Don W.: Observations On Two Patients With Paroxysmal Ventricular Tachy-

cardia Treated by the Intravenous .Administration of Quini’dine Lactate, .Am. Heart
J, 30: 276, 1945.

Clinical Reports

ANEURYSM OF THE DESCENDING THORACIC AORTA

Samuel A. Loewenberg, M.D., and Samuel Baer, M.D.

Philadelphia, Pa.

B ecause of the comparative rarity of aneuyrsms of the lower thoracic aorta
and because the diagnosis is frequently missed, we feel justified in discussing
this condition and reporting such a case. Most reported series of aortic aneurysms
are divided into three groups; that is, those of the arch, of the thoracic aorta,
and of the abdominal aorta. Of these, aneurysms of the descending thoracic
aorta are the least common.

Lucke and Rea,^ in their series of 321 aortic aneurysms, found that 173 were
in the arch, 40 in the abdominal, and 31, or 11.7 per cent, in the thoracic aorta.
Of these, the number of lower thoracic aneurysms were found to be compara-
tively few. Brindley and Schwab® stated that 2 per cent of aortic aneurysms
were found in the lower thoracic aorta, and Kampmeier® noted 30 of 633 aortic
aneurysms (4.7 per cent) were in the descending thoracic aorta. Levitt and
Le\^‘‘ reported about the same incidence; of ninet>'’-four aortic aneurysms, four
were found in the descending thoracic aorta.

Not only are these aneurysms of the thoracic aorta rare, but, because of their
location and because of the varied clinical pictures which they produce, they
may frequently remain undiagnosed during life. Nonetheless, a review of the
literature suggests that the clinical features and roentgen findings in most in-
stances are sufficiently characteristic to warrant the diagnosis of aneurysm of the
descending aorta.

CASE HISTORY

W. B., a colored man 61 years of age, complaining of abdominal pain, was admitted Feb. 11,
1944, to the Philadelphia General Hospital on the surgical service. The patient had been in his
usual state of health until Jan. 23, 1944, when he first noted weakness and general malaise and a
slight cough. A physician told him he had “flu" and recommended bed rest. About a week
after the- onset of the illness he began having abdominal pain. The pain was located in the upper
abdomen just above the umbilicus. It was dull but persistent and was aggravated by coughing
and deep breathing. The remainder of the present history was essentially negative. The previous
history revealed that in 1941, upon admission for a suprapubic prostatectomy, a strongly positive
Wassermann had been found.

The patient appeared quite comfortable. The temperature was 100.4'- F.; the pulse rate,
100 per minute; the respiratory rate, 20 per minute; and the blood pressure, 120/80. The other

From the IMedical Service of Dr. Samuel A. Loewenberg, Philadelphia General Hospital.

Received for publication Oct. 29, 1945.

653

654

AMERICAN HEART JOURNAL

significant findings were a few crackling rales in the right lower lung posteriorly and moderate
tenderness bilaterally in the upper abdomen. A tentative diagnosis of influenza or subacute
cholecystitis was made. On Feb. 12, 1944, a cholecystogram and a routine chest x-ray film were
negative. In view of the absence of physical signs and of significant laboratory findings suggest-
ing a surgical diagnosis, the patient was transferred to the medical service.

When first seen in the medical wards, the patient did not appear acutely ill. He continued
to run a temperature fluctuating between 99 and 102° Fahrenheit. Physical examination re-
vealed somewhat sluggish pupils, tremors cf the hands, an impaired percussion note, and a few
moist rales in the right upper lobe posteriorly. A diagnosis cf subsiding pneumonitis of the right
upper lobe was considered.

The Wassermann reaction was reported positive on two occasions. The interpretation of a
second cholecystogram done March 1, 1944, was "nonvisualization of thegall bladder." The spinal
fluid was found to be completely normal. Blood sugar and blood urea were normal, urine and
blood cultures were sterile, and agglutination studies for tj^phoid, paratyphoid, and undulant
fever were negative. -A blood count revealed 3,0D?,0D0 erythrocytes and 13,400 leucocytes, of
which 72 per cent were polymorphonuclear cells. .A gastrointestinal series was begun March
14, 1944. Upon fluo.-oscopy and roentgen study of the esophagus and stomach, it was noted that
the esophagus in its lower portion was displaced anteriorly and to the left by a mass lying anterior
and to the right of the spine. Fluoro.scopically this lesion appeared to be continuous with the
descending aorta. X-ray e.xamination of the spine showed suggestive evidence of erosion of the
bodies of the ninth and tenth dorsal vertebrae on the right (Figs. 1, 2, and 3). Based on these
findings a diagnosis of aneurjsni of the descending aorta was made. Because of the unusual dis-
placement of the esophagus, it was assumed that the aneurj'sni was located in the lower thoracic
aorta as it entered the hiatus of the diaphragm.

The patient’s condition became progre.«sivcly worse. His cough became more severe and he
expectorated bright red blood. The cough was present only in the morning and on one occasion
was accompanied by the expectoration of a cupful of briglit red blood. TJie temperature con-
tinued elev’atod, but with sedation the cough and hemoptysis subsided. On the morning of
Mardi 21, 1944, the patient was suddenly seized with a severe paroxysm of coughing with profuse
hemoptysis and died before a physician could reach his bedside.

Aiilopsy . — Autopsy was performed four hours post mortem. The body was that of a well-
developed, well-nourished, middle-aged Negro man. There was a suprapubic cystotomy scar.
Sliglit axillary and inguinal lymphadenopathy was noted.

.Approximately 250 c.c. cf clear, straw-cclorcd fluid were found in the right pleural cavity
and about lUO c.c. in the left pleural cavity. There appeared to be approximately from ISO to
200 c.c. of {Jericaniial fluid which was not well measured and about 750 c.c. of slightly opalescent
fluid in tlie peritoneal cavity. Tlicre were a few adhesions between the gall bladder and the
mesentery of the transverse colon. The peritoneal surfaces were otherwise smooth and glisten-
ing. The dome of the urinary bladder was adherent to the anterior abdominal wall beneath the
site of the cystotomy wound. The aorta showed tree-bark wrinkling throughout and many
athero'clerotic plaques. The mouths of the coronarj' arteries were widely patent. The ascend-
ing portion of the arch was somewhat dilated. .At the lowermost portion of the descending aorta
just above the tiiaplmigm. a large saccular aneurysm wa.s found. The ostium of the aneurysm
mc.asart'd 6 cm. in diameter and >eemed completely fillc-ri with a thrombus. The thrombus and
-ac me.'istircd 10 cm. in diameter and extended into the left pleural cavity, pressing upon the left
lower lobe. The pleura here was adherent to the aneurj'smal sac which had ruptured into the
Umg tissue at the ba«e of the sac. The heart appearcrl normal in size. The myocardium showed
gros- fibrosis. The aort ic valve cu*-ps were thin and mobile. The sinuses of Valsalva were some-
■uhat stretched due to dilatation of the aorta. The mitral valve leaflets showed a few thickened
a.-e.!**. The coronary arteries had a minimal amount of sclerosis but appeared normal other-
wise.

The left lung weighed 461 grams; the right, 5 grams. The lungs revealed smooth and
glistening pleur.al surf.aces, hene.ath which areas of hemorrhage could be seen. Thtre was a fine

LOEWENBERG AND BAER : ANEURYSM OF DESCENDING THORACIC AORTA 655

generalized emphysema which made the lungs pillowy to palpation. The sectioned surfaces
show'ed the bronchi to be filled wdth blood which w^as clotted. The pulmonary tissue showed
diffusely scattered blood-red areas due apparently to aspiration of blood in the alveoli. A probe
passed through the bronchus of the right lower lobe entered the area at the base where the aneurj’sm
had ruptured into the lung; this area was apparentl 3 '^ the source of the blood in the bronchial
tree. The pulmonarj-^ vessels were, patent.

Fig. 1. — Note the shadow', of the aortic aneurysm behind the cardiac silhouette.

The Spleen weighed 83 grams and w^as normal in size. Its sectioned surface showed the folli-
cular markings well against a blood-red pulp. The a.xillary, inguinal, and mesenteric lymph
nodes w'ere slightly enlarged and rubbery in consistencj'.

. The left kidney w^eighed 193 grams; the right, 170 grams. The kidneys appeared normal in
size. Their capsules stripped wdth slight difficulty to reveal a finely granular surface which re-
tained some degree of fetal lobulation and also show^ed a few-- small, red, shallow', depressed scars.
The sectioned surfaces showed congestion. The markings of the cortex and medulla appeared
grossly normal in outline and ratio. The renal pelves were thickened. The ureters showed slight
thickening of their walls. The right renal pelvis w'as subdivided and terminated in a double ureter
which united at a point approximately located at the edge of the pelvic brim. The urinary

656

AMERICAN HEART JOURNAL

bladder was adherent to the anterior abdominal wall. There appeared to be a scar on the left
side of t!ie bladder fundus. The bladder mucosa was congested. The left testicle was one-half
the si/e of the right, which appeared normal in size. There was a scar in the midline at the base
of the bladder extending into the prostatic urethra.

rie. 2, — .ts seen in the anteroiwsterlor view, the e^ophiiKus Is (llsplncotl to the loft and atiteriorly. The
shadow of the barlum-riin"<l esopliuRus has tjeon retouehtHl.

The esoph.agU" showed interesting findings; it had an S-shaped coiir-e. .\t the top cf the
ui)per edge of the aneurysm the e-ophagus was displaced horizontally, and at the lower portion cf
the anearV'-m the e-ophagus va^ pushed by it to the left. The stomach contained approximately
2.Sri c.c. of clotted blood. There were scat teretl petechiae and mucosal hemorrhages throughout
the intestines. TJic liver weighetl 1,200 grams and was congested. Its margins were slightly
rtnmdfsi. 'Ihe lobular markings were well defineil. There were a few adhesions around the gall
bladder. If contained normal, concentrated bile. The bile ducts were patent. The pancreas
appeared ratb.er large and firm but was otherv\i''e normal.

The adren.'ds appeared normal. The brain nas not removed.

Stimn'.ry, — (i) Syphilitic aneurysm of the descending thoracic aorta; (2) rupture of the
aneurysm into the left lung, fmphv<-enia; (3) distortion of the e'-ophagus; and (4) benign nephro-
tdc’ro'.is, he.di-d pjelonephn’ti'-, diniblc right ureter.

LOEWENBERG AND BAER; ANEURYSM OF DESCENDING THORACIC AORTA 657

Pig_ 3_ — In the right obliciue view, the anterior displacement of the esophagus is readily visible. The
shadow of the barium-filled esophagus has been retouched.

DISCUSSION

The varied abdominal syndromes produced by thoracic disturbances as a
whole, and by aortic aneurysms in particular, have been repeatedly reported.
Coronar}'- thrombosis, dissecting aneurysm, aortic lesions, pleurisy, pulmonary
malignancy, and pneumonia have all masqueraded as primar}^ gastrointestinal
disease. Loewenberg and March® reported on a patient with aneurysm of the
lower thoracic aorta in whom the sole symptom was peristent and intractable
hiccup., Interestingly enough, this aneurysm also occurred at the hiatus of the
diaphragm and was diagnosed premortem.

The anatomic relation of the esophagus to the aorta is of extreme importance
in diagnosing the lesion. Roesler® and others have emphasized the value of
determining the displacement of the barium-filled esophagus in cardiac roent-
genolog>^ Normally, the upper thoracic aorta occupies a position anterior and
to the left of the esophagus. As the aorta and esophagus pass through the hiatus

658

AMERICAN HEART JOURNAL

of the diaphragm, the esophagus crosses over the aorta, at this point being
anterior and somewhat to the left of the aorta. In the majority of aortic aneu-
rysms, the aortic extension is posteriorly and to the left,^ so that the esophagus
is displaced posteriorly and to the right. The only aortic aneurysm that can
displace the esophagus anteriorly and to the left is in an aorta at the hiatus.
Roesler®, Shanks, Kerley, and Twining,* and others®*'- have stressed this anatomic
relationship and have pointed out that this deviation of the esophagus may be
produced by one other rare aortic abnormality; namely, right-sided aortic arch.

Another finding of note was the erosion of the ninth and tenth dorsal verte-
brae. Many observers, in commenting on aneurj-sms of the lower aorta,
have emphasized the roentgen finding of destruction of the ninth, tenth, eleventh,
and twelfth dorsal and the first lumbar vertebrae. In the majority of cases of
aneurysm of the descending aorta, this is a nearly constant finding demonstrable
by x-ray examination.

CONCLUSIONS

1. The relative incidence of aneurj’^sms at various aortic sites is reviewed
and a case of aneurysm of the descending thoracic aorta reported.

2. The clinical and roentgen features of this rare aneurysm are discussed.

3. Gastrointestinal syndromes produced by this lesion are mentioned and
the relation of the esophagus to the aorta emphasized. Attention is also called to
erosion of the vertebrae produced by aneurysm of the descending thoracic aorta.

1. Liickc, B., and Rea, M. M.: Studies on .Aneurysm, J. A. M. A. 77: 935, 1921.

2. Brindlev, P., and Schwab, E, H.: .Aneurvsms of the .Aorta, Texas State J. Med. 2.5; 757,

1930.

3. Ivanjpmcier, R. H.: Saccular Ancurv'sm of the Thoracic .Aorta, .Ann. hit. Med. 12; 624,

1938.

4. Levitt, A., and Lew, D. S.: .Ancurvsm of the Thoracic and .Abdominal .Aorta, Am. J. Clin.

Path. 10; 332, 1940.

5. Loewenberg, S. .A., and March, H. C.: Persistent Hiccough-s as the Sole Symptom of Tho-

racic Aneurysm, Am. Hhart J. 13: 624, 1937.

6. Rocslcr, Hugo: Clinical Roentgenology of the Cardiovascular System, Springfiekl, 111.,

1943, Charles C. Thomas.

7. Luckc, B., and Rea, M. !L: .Studie.s on Aneurysm, J. .A. M. A. 81: 1167, 1923.

8. Shanks, S. C., Kerley, P. J., and Twining, E. W.: Textbook of X-ray Diagnosis, vol. 1,

London, 1938, H. K. Lewis & Co., Ltd.

9. Kird. H. J.: Right-Sided Aortic Arch, U. S. Nav. M. Bull. 42: 168, 1944.

10. Friedman, M.: Right-Sided .Aorta; Report of Two Cases. Radiology 2.5: 106, 1935.

U. Metygcr, H. X.. and Ostrum, H. \V.: Right Sided .Aortic .Arch, Am. J. Digest. Dis. 6: 32,

1939.

12. Ei‘en, D., and Taub. IL X.: Right Sided Aortic .Arch, Canad. M. A. J. 4.5: 402, 1941.

LL Putts, B. S., and Bacon. R. D.: Large .Aneurvsms of the Thoracic .Aorta, Am. J. Roentgenol.
35; 59. 1936. ^ -

HEART BLOCK CAUSED BY FAT INFILTRATION OF THE INTER-
VENTRICULAR SEPTUM (COR ADIPOSUM)

David M. Spain, M.D., and Richard T, Cathcart, M.D.

New York, N. Y,

The condition of “fatty heart,” which has also been called at various times
lipomatosis cordis, fatty infiltration of the myocardium, and cor adiposum, was
a frequent clinical diagnosis over twenty-five years ago. In more recent years,
this diagnosis has fallen into disrepute. Although it is true that “fatty heart”
only rarety causes actual clinical manifestations of disturbed cardiac function,
it is a definite entity that on occasion may not only be responsible for clinical
evidence of heart disease, but may also be the sole important factor leading to
the death of the individual.

Corrigan and Saphir* studied the anatomic changes in this condition. Their
report consists of an analysis of fifty-eight necropsied cases that revealed anatomic
evidence of fatty infiltration of the myocardium. Fat infiltration most likely orig-
inates from pre-existing, subepicardial fat. The usual site of infiltration is into the
myocradium of the right ventricle. At times the myocardium may be completely
replaced, or at least the few remaining fibers may be compressed as a result of the
fat infiltration. The left ventricle is only occasionally involved and never to any
significant degree. Isolated patches of fat are infrequently found beneath the
endocardium of the left or right ventricle. At times fat may infiltrate down from
the base of the heart into the interventricular septum. Because of the isolated
patches occasionally found beneath the endocardium, it has been postulated
that the fat originated not from direct infiltration, but as a result of transforma-
tion of pre-existing fibrocytes in situ into fat cells.

Corrigan and Saphir attributed the death of two of their patients solely to
the fat infiltration. In twenty-nine of their patients important contributory
symptoms were explained on this condition, while in the remaining twenty-three
it was considered merely an incidental finding. It should be noted that fat in-
filtration is not to be confused with fatty degeneration that is secondary to in-
fectious or anemic states.

The purpose of this report is to describe a case in which it is believed the
manifestations of heart disease that consisted of right-sided heart failure and
heart block were caused by fat infiltration of the right ventricular myocardium

■Rrom the Laboratory of Pathology, Bellevue Hospital, and First Medical Division, Bellevue Hos-
pital, (Columbia University, College of Physicians and Surgeons).

Received for publication Oct. 20, 1945.

♦Corrigan, M., and Saphir, O.: Fatty Infiltration of the Myocardium", Arch. Int. Med. 52: 410,
1933.

659

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AMERICAN heart JOURNAL

and the interventricular septum. A careful search through tlie literature has
failed to disclose any previously reported case of heart block caused by fat in-
filtration of the myocardium.

CASE REPORT

The patient, a 59-year-oIci white woman, housewife, was admitted to the First Medical Divi-
sion of Bellevue Hospital, May 9. I94f. with the complaint of difficulty in breathing: of five hours’
duration. For nineteen years prior to admission she had noted transient swelling of the ankles.
Recently this held been occurring at more frequent intervals and finally became constant. Twelve
years prior to admission, she had a single attack of precordial, knifelike pain that continued for
several hours. .\t that time her physician told her she had a heart attack and gave her digitalis
for several weeks. She has never again had a similar attack. During the last five years, she has
complained of frequent attacks during which “everything would go black, her heart would pound
hard and fast," and there would be difficulty in breathing. These attacks were irregular, occur-
ring either at rest or during activity, and lasted from several minutes to several hours. They
seemed to bo shortened following an injection by her physician; the nature of this injection could
not be ascertained. For the past two years, the difficulty in breathing became constant and she
was again given digitalis ^^hich she continued to take until this admission. The immediate episode
that brought her to the hospital began while she was asleep. She was awakened by palpitation
and dy.spnea of an extremely severe character.

Phx'sical e.xamination on admission revealed an extremely obese, well-developed, 58-ycar-old
white woman, slightly d\'spneic and cyanotic. The head and neck were normal The neck
veins tvere not engorged. The lungs were normal. The left border cf the heart was l.S cm. to
the left of the mid-sternal line with the apex in the fifth intercostal space. The heart sounds
Were extremely <listant with IL greater than Aj. There was a soft blowing systolic murmur heard
best .at the i>ase. The rate wa'' irregular and varied between 40 and 81; however, there was no
pulse deficit. The abdomen was obese but otherwise not remarkable: no organs were felt. Slight
pitting edema wa<! pre-ent in both lower extremities. The remainder of the physical examina-
tion reveale<l nothing of significance.

The temperature on admission wa« 99.4' F., the pulse varied between 40 and 80, and the blood
f»res‘-ure was I(>S/6S. The leucocyte count was 8.250, with 69 per cent polymorphonuclear leuco-
cytes. 30 per cent lymphocytes, and 1 per cent eosinophilic leucoextes. Hemoglobin (Sahli)
xva« 13 grams. E'mmination of the urine was norm.al. The erythrocyte sedimentation rate was
9 mm. in one hour. The Wassermann reaction was negative. The blood cholesterol was 286 me.
per cent. The basal metabolic rate 'vas plus 6 per cent. The patient’s weight was 187 pounds.
Benuus pres'^ure measured 140 mm. of water. The circulation time, arm-to-tongue, was 22 sec-
ond-; arm to iiing, 10 seconds. .\n electrocardiogram on admission showed marked Icft-.axi.s
dexd.ation; atiricuiar rate, 89; ventricular rate. 40; P-R-. 0.22 second; QRS, 0.12 seconds; Tj in-
vrjted (Fig. 1).

'Die patient respontied moderately well to bed rest. The edema lessened with diure.'^is.
rhi- (our-meuith '^tay in the hospital xvas characterized by many episodes that were apparently
‘•mnbir to the att.acks she had had prior to admission. These .attacks were of two types; each
:ux<i'npatued by a moderate amount of cyanosis. During one, however. «he would be mark-
f'ily .ipprehf'mivc and dyspneic without any change in physical signs. In particular, there would
ru! ch.inee in cardiac rate and no lo-s of rcn«-ciousnes=. The second type would be more severe.
During th. -e attacks the patient would become comato-e and the heart sounds would be almoM
-ibic to hc.ar. The heart rate on several ocrasions w.a- mnrkc-dly decreased, .\systolc xvas
n>wi r definitely notwl, and there vxere never any convulsive seizures. Following these latter
.jttark,, she p.ttient would Iw entirely normal after a pericKi of fifteen minutes and would lie
qua .1% ;n l-rd for m'.-t of the d.ay thereafter. The Iir-t typ.e of attack was -ometimes relieved bv
■’idxtsxe or a pl.->ri{)o ITe -ecom! tvpe w.i- relievt-d bv epinephrine. Reprated electrocardio-

SPAIN AND CATHCART ; HEART BLOCK CAUSED BY FAT INFILTRATION 661

grams revealed slightly variable but more or less constant heart block. The attacks first oc-
curred about cverj^ ten days, but the interval between them tended to become shorter, and oc-
casionally the attacks occurred several times in one day. Epinephrine relieved her for a time
but later was of no value. Barium chloride had a similar effect. The patient was then given
digitalis. Subjectivel.v she felt better. During the first day of digitalization she had several mild
attacks but thereafter was asymptomatic for two weeks. She then had a severe attack, folloAv-
ing which the electrocardiogram revealed a complete heart block with a ventricular rate of 22
(Fig. 2). Thereafter she remained asj'mptomatic for one week, apparently none the worse for

Fig_ — Electrocardiogram taken on admission revealing an auricular rate of 80 and

a ventricular rate of 40.

the slow heart rate. Finally, on the one hundred tenth hospital day, she e.xperienced another
severe attack from which she did not recover despite the administration of epinephrine, coramine,
and oxygen.

Post-Mortem Examination* (Necropsy No. 32655).— The body was that of a well-nourished,
extremely obese, elderly white woman, 5 feet, 3 inches in height, and weighing approximately
190 pounds. . Marked dependent lividity was present and there was slight edema of the ankles.

*Description is limited to the pertinent findings.

662

AMERICAN HEART JOURNAL

The panniculus was everv-where quite thick and golden yellow in color. The heart weighed 570
grams. Tlie epicardium was smooth and glistening, and there was a marked increase of sub-
epicardial fat. Fat e-vtended directly into the myocardium of the right ventricle and practically
replaced all of the muscle fibers. This also was present to an insignificant degree in the left
ventricle. Numerous sections through the intcr\'’entricular septum, particularly in the region
of the auriculoventricular node, revealed almost the entire myocardium to be replaced by fat.
No .similar change was present in the lower two-thirds of the interventricular septum. All of
the chambers were dilated and the walls were flabby. The valve leaflets were all delicate and com-
petent. The foramen ovale was not patent. The coronary ostia were widely patent and the
coronary arteries were without evidence of atherosclerosis. The aorta was not dilated or tortuous
and the wall was elastic. There were a moderate number of atheromatous plaques present.

rjc. ^.-.-Elrctrocardlograin taken two weeks after dlgUallzatlou reveaUnf: comjilcio heart block with

a ventricular rate of 22.

The hing.s were congested. The liver weighed 2,000 grams and the lobular architecture was
ncccntuatcd. The cut surface was deep red in color. The only other abnormal finding was the
abM'nce of l>oth ovaries and Fallopian tubes (surgical).

Ex.-unination of histologic sections from the right ventricle and interventricular septum dis-
closed almost complete replacement of the myocardial fibers by fat cells (Fig. 3). Wherever
myoecardial lilxTs (H-rsi^ted, they were markedly compressed. The final anatomic diagnosis was
olK-.itj” f.at infiltration of the myocartlium, most marked in the right ventricle and interventricular
yt-pttinr; enlirgenient of the heart; atrophy of the myocttrdiuin; chronic passive congestion of th
liver; congestion of tin; ‘.pken; edema of the lungs; edema of the anklc.s; absence of both tube
.and ovaries.

SPAIN AND CATHCART; HEART BLOCK CAUSED BY FAT INFILTRATION 663

Fig. 3. — Photomicrograpli of section taken through interventricular septum revealing extensive fat
infiltration vlth compression of remaining myocardial fibers (hemato.xylin and eosin. XSO).

DISCUSSION

Post-mortem examination of the heart revealed no evidence of rheumatic,
syphilitic, hypertensive, or arteriosclerotic disease. In addition, there was no
clinical evidence of avitaminosis or anemia, and the basal metabolic rate was plus
6. It, therefore, seems reasonable to assume that the clinical manifestations of
heart failure that were present for many years can best be explained by the
interference of the function of the right ventricle subsequent to the fat infiltration.
Although heart block does occur without any demonstrable anatomic change in
the heart, the extensive infiltration of the fat in the upper third of the inter-
ventricular septum undoubtedly played an important role in the development
of the heart block in this patient.

Fat infiltration of the heart is most commonly associated with obesity,
diabetes mellitus, and chronic alcoholism. In this particular case, the patient
was very obese with extensive deposits of fat beneath the epicardium in the
omentum and mesentery. This case differed somewhat in clinical course from
that of the usual case of "fatty heart” in that the heart failure was chronic,
and also in that heart block was present. On rare occasions the complete replace-
ment of the myocardium of the right ventricle may so weaken the wall that
rupture takes place.

664

AMERICAN HEART JOURNAL

SUMMARY

A case of extensive fat infiltration of the right ventricle and interventricular
septum of tlie heart is presented. *

The clinical manifestations of chronic right-sided heart failure and heart
block is attributed to this anatomic change.

SYPHILITIC GUMMATOUS AORTITIS AS THE CAUSE OF CORONARY
ARTERY OSTIAL STENOSIS AND MYOCARDIAL INFARCTION

Report of a Case

Tobias Weinberg, M.D., and Heinz F. Beissinger, M.D.

Baltimore, Md.

A LTHOUGH syphilitic aortitis per se is frequently observed at necropsy,
^ the gummatous type of involvement is admittedly rare.^’“ Furthermore,
the association of coronary artery ostial stenosis and myocardial infarction is
itself uncommon,^ so that this association in a case of gummatous aortitis makes
the following case even more unusual and prompts its report.

CASE REPORT

J. G., a white woman, aged 28 years, was admitted to The Sinai Hospital complaining of
shortness of breath. Members of her family contributed the information that the patient had
had a “cold” for several months and a cough for at least si.\ months. According to the patient’s
story, she was well until four weeks before admission when she suddenly became extremely dyspneic
after walking several blocks. The dyspnea was associated with aching pain in the right shoulder.
From then on she had recurrent episodes of dyspnea upon exertion. About three days before
admission she began to cough. Two days before admission her temperature became elevated
and rose as high as 104° Fahrenheit. On occasion she had substernal pain which radiated to the
right shoulder and to the right and left arms. The night before admission she expectorated blood.
On the day of admission the sputum was observed to be brown. The positive findings were as
follows :

Physical Examination . — The positive findings were as follows: Temperature, 102°; pulse,
140 per minute; and respirations, 32 per minute. The blood pressure was 90/74. She was obese.
She was dyspneic and the mucous membranes were cyanotic. There was dullness to percussion
posteriorly at the base of the right lung. Numerous rales were heard in the same area, as well
as'in the right upper and left lower lobes. The heart was found to be normal in si/e. The heart
sounds were distant and the rh 3 'thm was regular. A sj-stolic murmur was heard in the mitral
area.

Laboratory Studies . — The red blood cells were 3.89 mdlion per cubic millimeter; hemoglobin,
11.7 Gm.; and white blood cells, 23,800, of which 82 per cent were of the neutrophilic series. The
blood urea nitrogen was 80 mg. per cent. The carbon dioxide combining power of the blood
was 78.2 volumes per cent. Examination of the sputum failed to reveal the presence of an\’’
pneumococci. Blood for a Wassermann test was not obtained.

Course in Hospital . — The condition of the patient became rapidh^ worse. The blood pres-
sure and pulse became unobtainable. Digitalis therapy w'as instituted, follow'ed bj”^ sulfathiazole
and adrenal cortical e.xtract. Therapy’’, how'ever, was ineffectual and the patient died less than
twenty-four hours after admission. The clinical impression wns bronchopneumonia. The
terminal temperature was 106° Fahrenheit.

From the Laboratories of The Sinai Hospital, Baltimore, Md.

Received for publication Nov. 26, 1945.

665

666

AMERICAN' HEART JOURNAL

N^acropsy Findin^is . — The autopsy was performed alniOft four hours after death. The con-
tributory findings nere as follows; The heart was not enlarged and weighed 250 grams. Both
veiitricle-s were moderately dilated. The myocardium of the left ventricle was yellowish-brown
with distinctly yeOowish areas visible in the papillary muscles. The valve leaflets and cusps
were not remarkable, .\rising within the sinuses of Valsalva, corresponding to the right and left
aortic cusp‘=. there was a broad plaquelike area of thickening upon the intimal surface of the aorta
which measured approtvimaltly 3 by 2 centimeters. It completely encircled and narrowed the
orifice of the left main coronary artery and also encroached upon the orifice of the right main
coronary artery but did not encircle it (Fig. 1). Beyond their orifices the coronary arteries were

Kik l. — ne.iri opfiiwl to show aortic valve and eiicroaclmient upon coronary
artery ostl.T by plaque at base of aorta.

r.ideb pslettt ami thin-walled. The aorta contained two more plaquclike area'- of somewhat
•• md!< r ^i -e tn the .I'-cending and tranver'-e arches of the aorta. The remainder of the aorta was
ri.-.-tic -md cotuaineti only scattered atherosclerotic streaks. There was about 200 c.c. of clear,
'traw-roloreii fluid in the right pleural cavity and 300 c.c. of a similar fluid in the left pleur.il
tatjTv. The jurfact's of tiic lungs showed cxtcnsi\c edema.

WEINBERG AND BEISSINGER; SYPHILITIC GUMMATOUS AORTITIS

667

Fifr. 2.

Fig. 3.

Fig, 4.

Fig. 2. — Section of myocardium of left ventricle shoving infarction.

■ Fig. 3. — Section through plaque at base of aorta showing gummatous alteration.

- . Fig. 4. — A, Section of aortic plaque showing areas of medial destruction with fibrous replacement
and plasma cell and lymphocytic infiltration. B, Weigerfs elastica-van Gieson stain of portion of plaque
in aorta showing marked destruction of the elastic tissue in the media.

668

AMERICAN HEART JOURNAL

Microscopic FhidiuRs . — The sections of flic myocardium taken from the posterior wall as
v.e!l as from the papillary muscles of the left ventricle showed tinctorial changes, loss of cross-
striations. and areas of extensive necrosis with dense polymorphonuclear infiltration (Fig. 2).
The sections of the large plaques observed in the aorta showed a marked intimal thickening, con-
sisting partlv of cellular and partly of collagenous connective tissue within which there were large
areas of necrosis as well as fibrinoid degeneration. The areas of necrosis assumed a granular
amorphous basophilic character and, in some instances, were in pro.ximity to large collections of
plasma cells and lymphocytes (Fig. 3). In some areas the media was practically completely de-
.‘•troj'cd with resulting fibrous replacement and plasma cell infiltration (Fig. 4). Many blood
vfs'-els in the media and adventitia were surrounded by collections of plasma cells and lympliocytes,
and <=ome showed a cellular intimal proliferation. The adv^entitia in these areas was thickened.
Stains for spirochetes performed by both the Levaditi and Dieterle techniques failed to reveal
their presence. Sections of the other organs merely confirmed the gross observations.

COMMENT

According to Held and Goldbloom‘ and Gordon, Parker, and Weiss," only
a few cases of gummatous aortitis have been reported in the recent literature.
The first-mentioned authors claim to have found only three instances in their
review of the literature. Gordon and co-authors, in a review of their own cases,
found eight instances of gummatous alteration in a series of 360 cases of sj’^philitic
aortitis.

Both Burch and Winsor'* and Love and Warner'* have made e.xtensive analyses
of the association of coronary ostial stenosis due to syphilitic aortitis and acute
m 5 '’ 0 cnrdial infarction. The former® found three of a series of 185 myocardial
infarctions to be due to syphilitic coronary arter>' ostial stenosis, and accordingly
concluded that myocardial infarction as a result of syphilis is rare. In a series
of 193 cases of syphilitic aortitis they found forty in which there was narrowing
of the ostia of one or both coronary arteries. Of the.se, only three had myocardial
infarction. Love and Warner^ analyzed their series of fifteen cases in which there
was stenosis of either one or both coronary ostia. In eight of the fifteen cases
there was marked fibrosis of the myocardium. In four cases there was acute
myocardial infarction as evidenced by leucocytic infiltration. Corrigan,® in
his discussion of myocardial infarcts and syphilitic aortitis, stated that mor-
jihologic evidence was rarely demonstrated at the post-mortem e.xamination.
Von Glahn'-* collected 687 cases of syphilitic aortitis and found among them 1 20
instances of occlusion or stenosis of one or iioth coronary artery orifices and only
four infarcts of the myocardium.

Most authors emphasize the relatively early age at which syphilitic coronary
artor>' stenosis is found. Bruenn® gives the average age as 34 years. Burch
and Winsur® place the average age at 40 years. The youngest case they found
was in a person 20 years of age, Gordon, F^arker, and Weiss’" youngest patient
with gummatous aortitis was 32 years old. Clawson® reported only one case
occtirring in the third decade. Other authors® ' report cases in patients in their
thirtie.s hut none younger.

!-rom the foregoing brief review of some of the pertinent literature on the
‘ubjert. it is obvious that the jtre.sent case is an instance of syphilitic aortitis

WEINBERG AND BEISSINGER: SYPHILITIC GUMMATOUS AORTITIS 669

associated with coronary ostial stenosis in an individual manifesting the effects
of the disease at an even earlier age than that most commonl}’^ recorded in the
literature. The findings of acute myocardial infarction in our case places it in
another group of relatively rare observations. The same is also true of the
finding of gummatous aortitis.

The microscopic findings in our case are so characteristic that in spite of the
lack of corroborative evidence in the form of a positive serologic test for syphilis
or the finding of spirochetes, we feel quite certain of the etiologic character of the
aortic lesion described.

SUMMARY

A case of syphilitic gummatous aortitis is reported occurring in a 28-year-oId
woman and associated with coronary artery ostial stenosis and acute myocardial
infarction.

Attention is called to the rarity of each of the findings individually and as a
group, particularly in an individual in the third decade of life.

REFERENCES

1. Held, I. W., and Goldbloom, A. A.: Cardiovascular Syphilis With Special Reference to

Syphilis of the Aorta, Urol. & Cutan. Rev. 47: 28, 1943.

2. Gordon, W. H., Parker, F., Jr., and Weiss, S.: Gummatous Aortitis, Arch. Int. Med. 70:

396, 1942.

3. Burch, G. E., and Winsor, T.: Sj'philitic Coronary Stenosis With Myocardial Infarction,

Am. Heakt J. 24: 740, 1942.

4. Love, W. S., Jr., and Warner, C. G.: Observations Upon Syphilis of the Heart, Coronary

Ostia, and Coronar}" Arteries. II. With Special Reference to the Myocardial Lesions
Noted in Stenosis of the Coronary Ostia, Am. J. Syph. & Neurol. 18: 154, 1934.

5 Corrigan, M. C.: Myocardial Infarcts and Svphilitic Aortitis, Urol. & Cutan. Rev. 45:
229, 1941.

6. Bruenn, H. G.: Syphilitic Disease of the Coronary Arteries, Am. He.\rt J. 9: 421, 1934.

7. Pincoffs, M. C., and Love, W. S., Jr.; Observ’^ations Upon Syphilis of the Heart, Coronary

Ostia and Coronary Arteries. 1. With Special Reference to the Clinical Picture
Presented by Svphilitic Stenosis of the Coronar\^ Ostia, Am. J. Syph. & Neurol. 18:
145, 1934.

8. Clawson, B. J.: Syphilitic Heart Disease. Urol. & Cutan. Rev. 45; 219, 1941.

9. Von Glahn, W. C.: Changes in the Coronary Arteries in Syphilis. From Lamb, A. B., and

Turner, K. B.: Cardiovascular Syphilis, New York, 1921, Nelson Loose Leaf Living
Medicine, vol. IV, p. 346. \

Abstracts and Reviews

Selected Abstracts

Linrlqin.‘'t, T. : rntorniittcnl Claudiciilion and Vasciilnr Spasm: I. Is Vascular Spasm
n Conlriliutory Cause of Intermittent Claudication in Patients With Structural
Disease of the Arteries? Acta rued. Scandinav. 121:32 (I), 1945.

Tlie autlior investigated the mechanism of the cutaneous pallor and coolne.ss observed during
attacks of intermittent claudication in an attempt to determine whether this represented a true
v'a.sospasm with reduction in muscle blood supply or whether it was simply the excessive cfTcct
on organically narrowed vessels of the slight cutaneous vasoconstriction that has been described
in nonnal persons in association with exercise.

Oscillometric records were made on eight patients with intermittent claudication. The
cutT was applietl to the thigh or upper calf rather than the ankle since it was felt that most of the
muscular branches of arteiies were given off above the latter point and that measurements at the
ankle might reflect cliange.s in vessels supplying mainly skin or supporting structures. .‘\ special
apparatus wa.s used to record the relatively small pulsations of the thigh and calf.

It wa.s found that the amplitude of pulsations decreased markedly in some patients when
cramps appeared but in others the amplitude increased in a fashion similar to the normal response.
The occurrence of these two types of reaction appeared to be independent of the integrity of the
sympathetic supply to the limb, for both occurred in patients with and without previous lumbar
sympathectomy or block.

The possibility that the diminished oscillations were due to less blood reaching the more distal
musclc.s because it was being “stolen” by more proximal muscles was considered and rejected.
It was conclufled that true va.sospasm did occur in .‘;ome patients with intermittent claudication
but not in all and that it was independent of the .sympathetic innervation of the affected limb.

S.\\T.N.

(>rjffiil». G. C., and Hailey, K. T. : Tl«c Treatment of lUieumatic Fever by Ilocnlgcn
Uay Irradiation. .'\nn. Int. Med. 21:1039 (June), 1946.

Hiis report conccrn.s e.xpcrienccs gained from irradiation therapy among 201 patients in the
rhfum.-Jtlc fever unit at the U. S. Naval Ho.spital, Corona. California. .All the patients had been
ill with rhcmnatic fever which had been present for six months or more. The patients were divided
into three groups, I hose in the first group received 100 roentgens through the myocardium at
t\cckly interv.als for five sticccssive weeks. Those in the second received 100 roentgens through
the myiK'.irdium and over the middle and lower cervical sympathetic ganglia every week for five
succc-vjve weeks, the p.itients in the thin! group received no treatment but went through the
*ame mechanical routine a.s did those in Groups I and II fa lead filter was used to block out the
cctatgen re-.tilts of this program were carefully analysed. It was concluded that

t a fp ,va« no greater improvement in the patients trentetl than in those who did not receive irradi-
Adon I icrape 1 here wa>, no demonstrable therapeutic value from roentgen ray therapy in the
t rinnry or sn t le retur.'-eni .attacks of rheumatic fever. The final conclusion is that roentgen rav
u-^r.ipy not a useful prfKvdure in the treatment of rheumatic fever. \Vr;.vnKOS.

070

SELECTED ABSTRACTS

671

Jones, M., and Scarisbrick, R. : The Effect of Exercise on Soldiers With Neurocirculatorv

Asthenia. Psychosom. Med. 8:188 (May-June), 1946.

The influence of effort syndrome on the reaction to exercise was studied at the Mill Hill
Hospital, London, England. Effort syndrome was classified into three groups: (1) where poor
physical endowment is the primary factor in producing symptoms; (2) where poor physical en-
dowment is the primar\' factor in producing symptoms but the patient responds in a neurotic
manner to his constitutional inferiority; (3) primarily neurotic. Since the hospital is a neurosis,
center, patients belonging to Group 1 were rarely seen.

Comparisons were made of the effects of exercise on thirty-five normal control subjects,
twenty-five patients Avith effort syndrome in Group 2, and ten patients with effort syndrome
in Group 3. The subjects undertook two tests: standard work, in which they pedaled a bicycle
ergometer for five minutes, and maximal work, in which they pedaled to the point of exhaustion
in ten minutes. Observations Avere made on the pulse rate and blood lactate leA'el.

The patients Avith effort syndrome in Group 2 (constitutional) shoAved a mean blood lactate
rise of 28.9 mg. per cent after standard exercise. The corresponding figure for the normal con-
trols AA'as 21.1 mg. per cent. The patients in Group 3 (psychogenically produced effort sjmdrome)
shoAved a blood lactate rise similar to that of those in the control group. The pulse rate response
to standard AAmrk AA’as a greater rise and a sloAA'er decrement in those in the effort syndrome group
than in those in the control group. Group 2 patients had a higher rise and a slower decrement than
did the Group 3 patients.

After maximal Avork, the mean blood lactate rise for the control group was 78.0 mg. per cent
and for the patients AA'ith effort sjmdrome, 50.2 mg. per cent. The mean lactate rise Avas essentially
similar for the patients AAuth effort syndrome in both Groups 2 and 3. The pulse rate response
to maximal AA'ork, in contrast to the effect of standard AA'ork, AA'as similar in both patients and nor-
mal controls.

It appeared from these obserA'^ations that a satisfactorA^ differentiation betAA'een Group 2
(constitutional) and Group 3 (psychogenically produced) effort syndrome can be made on the
basis of the blood lactate response to standard exercise. When maximal exercise is used, it is
evident that patients Avith effort syndrome, unlike the normal controls, giA'e up exhausting physical
AA'ork before a "physiological” end point is reached, due to Avhat amounts to effort phobia.

Laplace.

Westermark, N.; A Method for Determining the Blood Pressure in the Pulmonary

Artery. Acta. Radiol. 26:302 (No. 3), 1946.

By making multiple roentgenograms of the chest in subjects performing a modified Valsah'^a
experiment by bloAA'ing into a closed system in Avhich pressure was measured, a point AA'as found at
AA’hich a marked diminution in the diameter of the pulmonary vascular shadoAA's appeared. In
tAA'enty normal subjects this phenomenon occurred at a pressure of 25 to 30 mm. of mercury.
This AA'as belieA’-ed to approximate closely the systolic pressure in the pulmonary arterial system.
Ninety patients Avith mitral stenosis AA'ere studied in a similar manner. TAventy-tAA'o of these had
clinical signs of a mild valvular lesion and shoAA'ed pressures AA'ithin the normal range. In thirty-
patients AA'ith moderate mitral stenosis the pressures ranged from 30 to 60 mm. of mercury, AA-hile
thirty-eight Avith severe mitral stenosis required a pressure of oA-er 60 mm. of mercury to produce
significant decreases in the size of their pulmonary vascular shadows. It is believed that this
rnethod is a satisfactory- nonsurgical procedure for determining pulmonary blood pressures in man.

Sayex.

Pereira, A. do Sousa.: The Innervation of the Veins; Its Role in Pain, Venospasm and

Collateral Circulation. Surgery 19:731 (May), 1946.

The nerve supply to the veins contains afferent sensorA' pathAA-ays in addition to the efferent
vasomotor components. Mechanical or chemical stimulation of the A-eins causes pain. The
relief of venous pain and venospasm in acute phlebitis and thrombophlebitis by the injection of I

672

AMERICAN HEART JOURNAL

per cent novocain into the affected vein, or Ijy the anesthetic block of the sympathetic chain,
iasi>^ for a lonRcr period than the anesthetic action of the drug can account for. This suggests
that venospnsm may play an important role in the mechanism of pain. Venography in the author’s
cases demonstrated that venospasm extended far beyond the phlcbitic or thrombosed vein.
This venospasm may be relieved by peripheral anesthe.sia of the venous wall or by interruption
of the efferent pathways of the sympathetic chain.

I n cases of thrombophlebitis it was observed that repeated anesthetic blocks of the .sympathetic
chain with procaine hydrochloride, perivenous sympathectomy, or resection of the regional sympa-
thetic chain was followed by an increase in collateral venous circulation. These investigations
have demonstrated that physiologic or anatomic interruption of the innervation of the veins may
relieve the pain and the venospasm and also increases the development of collateral circulation.
The facts observed suggest that the plan of the innervation of the veins in relation to pain, spasm,
and collateral circulation is similar to that of the afferent sensory and the efferent vasomotor
pathways of the arteries. Naide.

Guthrie, D., arid Gapnon, G.: I'lie Prevention and Treatment of Posl-Opcralivc Lym-
phedema of the Arm. .Ann. Surg. 12.3:925 (May), 1946. . *

Tlic mo'it important factor in prevention of lymphedema of the arm following radical mastec-
tomy is the avoidance of infection. Prolonged immobilization of the arm following the operation
siiould be condemned. .Xijsolutc free and early mobilization should be instituted. It is as im-
portant to mobilize the arm following radical mastectomy to prevent edema as it is to exercise the
legs for prevention of phlebothrombosis and thrombophlebitis following operation in the pelvis.
The patient is retiue.sted to move her arm as soon as she reacts from the anesthesia. If roent-
genotherapy is indicated, one should avoid a destructive type of dermatitis.

The author^ recommend treatment of post-operative lymphedema by the Beck operation.
Five strip.s of celloidin are inserted into the subcutaneous tissue and left in place for three weeks.
This procedure aids in the development of collateral channels The Kondoleon operation has
proved to be of no value. Naide.

Stead, F,. A., .fr., Brannon, F. S., nnd Brannon. .J.; Concentrated Human Alhuniin
»n the I’roatinrni of Shock. .Arch. Int. Med. 77:564 (Mayl, 1946.

Tests of the usefulness of human albumin as sul)stitutcs for plasma have been made by observ-
ing the effects of giving it intravenously to seven normal suljjccts and thirty-four patients with
circulatory failure. The following studies were made on the.se .subjects: moan atrial pressure, oxy-
gen consumption, rrptical recording of arterial pre.ssurc, oxygen content of arterial and right atrial
blood, cardiac outfuit, plasma volume, and hematocrit.

No untrnvard effects were noted. None of the patients experienced chills, fever, urticaria,
pulmonary edema, or circulatory collapse.

Seven normal subjects received 1 liter of a 5 per cent solution of human albumin intravenously
within a irericKl of fifteen to thirty-one minutes. Two consistent changes were noted. The atrial
pressure aUv.ays ro<e and the hematocrit reading and concentration of hemoglobin always fell.
Hie .irierial pressure, I'ardiac rate, consumption of oxygen, and arteriovenous oxygen difference
showed no consi-tent change.

Stmlie-, were .d-'o rnarle on thirteen patients with circulatory insufftciencx- following acute
hrmorrhage. on -^iwen additional patients following injuries to the chest, and on two patients with
hfmofH-rir.irdium re-^ulting from tionetrating wounds. i\ll but two of tliese patients received
.''0 (,tn. of ft 25 fv. r cent -olmion of human allmniin. The re.sults of therapy in patients witli hemor-
ch.-igo v.'cre untfo.-ntly g(>r«4. The results of thempy in the patients with burns, dehydration, and
infertion were wui-fartorv.

1 he avi-raec inrrivjij- fjf plastna volume prcKhiced by 1 Gm. of alliumin wa.s 14 cc. .Although
aTbumin^ not (he tre.'Ument of shwk ns is whole bloorl, alhuniin is nevertheless an

ev.rrn.iiv uv'ful -.ub'-titute for p!.\-ma. From the standpoint of speed and convenience of ad-

SELECTED ABSTRACTS

673

ministration, convenient packaging, small bulk, stability under varying temperatures, and
absence of bacterial contamination, concentrated albumin is ideal. In civilian practice where
whole blood and plasma are readily available, albumin may not be used extensivelj' in the treat-
ment of shock. Under the conditions of war, concentrated albumin has many advantages.

Bellet.

Ik

Flett, D. M., and Powell, W. N. : Acute Bacterial Endarteritis. J.A.M.A. 131:397

(June 1), 1946.

These authors present what they consider to be the first report of endarteritis of the ductus
due to Diplococcus pneumonia. This infection was arrested on the thirteenth day after a total of
3,875,000 units of penicillin had been given within a period of twenty-eight days. At a later date,
the patent ductus was ligated. Six months after the original observation the patient had gained
25 pounds in weight and the auscultator}-’ phenomena previously’ observed were no longer present.
The patient was apparently well ten months after the original period of treatment.

Bellet.

Segers, M.: A Study of the Gaskcll Effect. Arch, internat. de pharmacodyn. et de therap.

71:173 (Nov.), 1945.

One of the most typical actions of the vagus nerve on the heart is that of producing positive
variations of polarization, known as the Gaskell effect. In order to determine the factors involved
in' this phenomenon, a study was made of the action of acetylcholine on the electrical charges on
the surface of the myocardium of the frog: in the rhythmically beating heart the positive poten-
tials are due to the disappearance of late negative potentials: in the nonbeating heart, acetylcholine
does not produce any positive variation. The Gaskell effect results, therefore, not from a modifi-
cation of the current of demarcation of the myocardium, but from a modification of the evanescent
state of polarization represented by the after-potentials. The action of adrenalin is identical but
is opposite in direction.

The Gaskel effect is often regarded as the factor responsible for the inhibitory action of the
vagus. This view is acceptable but it must be understood that the mechanism is not the only
one involved since the cardio-moderator effects of the vagus can occur in the absence of any varia-
tion of polarization.

The late negativity of the heart is accompanied by a postsystolic contracture occupying the
inter\’al which separates the beats. Under the influence of acetylcholine, the postsystolic con-
tracture disappears at the same time as the late negativity. Acetylcholine does not, however,
produce any change in tonus in the resting heart.

The after-potentials demonstrate the existence of a state of supernormality produced by the
heart beats and suppressed by acetylcholine. The Gaskell effect corresponds, therefore, to sup-
pression of a state of excitation and not to a true inhibition of the heart.

Laplace.

Wallace, L., Katz, L. N., Langendorf, R., and Buxbaum, H.; Electrocardiogram in

Toxemias of Pregnancy. Arch. Int. Med. 77:405 (April), 1946.

The authors discuss the presence of electrocardiographic changes during toxemias of preg-
nancy. Their series included twelve cases of toxemia of pregnancy without eclampsia. Group I
consisted of two patients who developed acute left ventricular failure at the time of labor. Group
II was made up of four patients who manifested no heart failure but presented electrocardiographic
changes. Group HI consisted of six patients in w'hom there was no evidence of heart failure and
in whom no electrocardiographic abnormalities were observ’ed despite the presence of toxemia.

. \ In Group I, electrocardiographic changes were observed which were characterized by inverted
T \yaves in Leads I^ CFs, and CF 4 and by the absence of any pronounced S-T deviation or changes
in the QRS complex. In one of the patients, complete restitution to normal occurred within

674

AMERICAN HEART JOURNAL

fsftwn wceki.; the other could not l>e followed. The authors suggest that the changes obsereed
in patients with to.vcmin who experienced cardiac failure simulate rather closely the changes
occa‘:iona!ly seen in acute nephritis.

In Group 11, during the last trimester of pregnancy, inversion of the T wave in CFj and CF^
was present; this reverted to normal within one week following deliver}-. Similar findings were
occasionally observed in normal persons as well as in patients with toxemia of pregnancy.

The possible causes of thc«c electrocardiographic abnormalities are discussed.

Beli.kt.

Merrill, A. J.s Etlcnin and Decreased Ilcnal Blood Flow in Patients With Chronic Con-
fie^stivc Heart Failnre: Evidence of “F<»rward Failure*' as the Primary Cause of
Edema. J. Clin. Investigation 2.5;.389 {Ma}-), 1946.

In patients with chronic congc.siive heart failure the cardiac index (liters per square meter
per minute) tends to f>e lower than average normal. These patients also exhibit a reduction in
renal plasma flow, glomerular filtration rate, and sodium clearance.

Renal venous congestion is not responsible for the reduced renal plasma flow because no
correlation i.s found to exist between the level of venous pressure and the volume flow of blood
through the kidneys. On the other hand, a significant correlation is found between renal plasma
flow and the cardiac index: that is, when cardiac output is reduced, renal plasma flow is reduced
{frequently to a greater extent than the cardiac output). .Associated with the reduction in renal
plasma flow is a significant decrease in sodium clearance which is accounted for chiefly by a low
filtration rate rather than by increased tubular rcabsorption of sodium. Sodium retention then
leads to edema formation.

The data indicate that “forward” rather “backward" failure is the cause of edema formation
in chronic congestive heart failure despite the fact that many patients have cardiac indexes
which fall well within the normal range. This apparent di.screpancy is explained by suggesting
that no absolute level of cardiac output exists below which patients develop cardiac failure;
the patient with thyrotoxico'-is may have a normal or increased cardiac index and still develop
congestive heart failure if the cardiac index fails to meet metabolic demands.

Friedi.and.

Zeek, P. M,: Heart AVciplit; H. The Kfiect of Tuberculosis on Heart Weight, Arch.
Path. 41:526 (May), 1946.

' The author points out that emaciation in tuberculous patients and not tuberculosis per se
i« the important factor f(ir the common finding of a small heart. In the ptc.scncc of a well-main-
tained nutrition, a tuberculous patient should have a heart of normal weight.

Gouekv.

PostolofT, A. V,, and Cannon, W.: Gene.sis of .Aortic Perfornlion Secondary to Car-
einoina of the Esophnpu*:. .\rch. Path. 41:553 (May), 1946.

To the total serie.s of sLviy cn«es reported to date, the authors add two of their own cases of
perfo.Mtion of the aorta by carcinoma of the esophagus. In both of those women, aged 76 and 38
ye.tr.-!. respectively, there was a historv- of progres';ivc dy.sphagia and sudden death preceded b\’
Iwmnrrhare from the no'^c and mouth.

Nerropjv nrvealed that the wall of the aorta had become undermined, leading to small
tntimal p^rforationv, not benuise of actual tumor cell invasion of the media and intima, but as a
rt'sult O’, cellular infiltration of the vaso v.a<mrum with socondarv thrombosis and fibroblastic
fcartion in the vo-cL. ' Goui-ev

SELECTED ABSTRACTS

675

Wexler, J., Whitlenberger, J. L., and Himmelfarb, S.: An Objective Method for De-
termining Circulation Time From Pulmonary to Systemic Capillaries by tbe Use
of tbe Oximeter. J. Clin. Investigation 25:447 (May), 1946.

The oximeter is an instrument which measures continuously the oxygen saturation of arterial
blood by means of photoelectric colorimetry of the intact fully flushed ear. The interval between
the beginning of a deep breath of 100 per cent nitrogen and the beginning of the downward de-
flection of the recording device (a galvanometer) was considered to be the time required for the
unsaturated blood to pass from the lungs 'to the ear. In thirty-five subjects without heart disease
the range of values was 4.1 to 7.0 seconds with an average value of 5.2 seconds. Twentj'^-three
subjects (66 per cent) were within the range of 4.6 to 5.5 seconds and the variation on repeated
tests in any individual did not exceed 1.8 seconds. Of course the recorded values are probably
higher than the true pulmonar}' to systemic capillar}' circulation time since the measurement
includes the time of inspiration, diffusion time of the nitrogen in the residual air, the galvanometer
lag, and the reaction time of the observer. The method promises to be useful and accurate in
that it is objective, requires a minimum of cooperation on the part of the patient, and eliminates
the variable arm-to-lung segment in the usual method of measuring the circulation time.

FRIEDL.A..^D.

Ileymans, C., and Capet, L. ; Tbe Influenee of Magnesium and Calcium on tbe Pro-
prioceptive Regulation of Arterial Pressure. Arch, internat. de pharmacodjm. et de

therap. 51:164 (Nov.), 1945.

It is well known that magnesium has a depressant action on the central nervous system which
can be neutralized by calcium. On the other hand, calcium deficiency has been shown to cause a
diminution of the aortic and carotid sinus reflexes which control the proprioceptive regulation of-
arterial pressure. An investigation was therefore made of the reciprocal influences of magnesium
and calcium on the vasomotor reflexes originating in the carotid sinus and of the action of calcium
on arterial hypertension produced by suppression of the four aortic and carotid sinus nerves. The
studies were performed on dogs and led to the following conclusions:

1. Magnesium sulphate can depress and almost paralyze the vasomotor reflexes concerned
in the proprioceptive regulation of general arterial pressure.

2. Calcium chloride or thiosulphate can re-establish the vasomotor reflexes of the carotid
sinus which have been depressed or paralyzed by magnesium.

3. Suppression of the four depressor nerves produces a substantial hypertension which
may be permanent or transient. The fall of arterial pressure after hypertension is produced by
suppression of the depressor nerves is due to cardiovascular collapse caused by the hypertension.

4. Calcium administered intravenously protects the heart against the effects of sudden
hypertension produced by suppression of the four depressor ner^'es.

5. Calcium administered intravenously, on the one hand, stimulates the heart but, on the
other hand, increases and maintains the hypertension produced by suppression of the depressor

Laplace.

nerves.

Book Reviews

I’lsoKOCARinoGRArntE, Auscultation- Collixtive (Acoustique— Tixiinique — Clinique).

Ry C. Lian, G. Minot, and J. J. Welti. Paris, 1941, Masson & Cic, 2,53 pages.

This monograph on phonocardiography represents years of \vork on thi.s subject bv the
authors. It is complete in scope and quite extensive in detail. In the first place, there is a dis-
cussion of principles of physics involved in the recording and Interpretation of heart sounds;
this is followed by a detailed description of the various apparatus u.=ed in making their studies of
heart sounds, venous pulse, and apex impulse. They have been able to record simultaneously the
electrocardiogram, the phonocardiogram, the venous pulse tracing, and the electrokymogram
or tracing of the apex impulse. Further, in the mechanical domain, thev have developed a good
method for recording heart sounds on phonograph records and for their rendition over a loud
speaker for the benefit of group auscultation. In addition to the studies on cardiology, they
present a chapter on recording of vascular murmurs and another chapter on the recording of
sound tracings of re.'jpiration and of abdominal ascit'c waves producwl by percussion.

For students of cardiologx- this monograph will serve as a work of reference and as an impor-
tant painstaking contribution to the special literature of the subject of phonocardiography. The
chapter.® on doubling of the first and second sounds, on the third .sound, and on g.allops are well
written and well illustrated with many figures.

WlLl.I.XM C. Kuzell, M.D.

Tiir. Venous. Pulse and Its Graviiic Recordi-ng. By Franz M. Grocdel, M.D. New York.

X. Y., 1946, Brooklyn Medical Pre.ss, Inc., 223 pages.

This book describes the author’s experience in recording the venous pulse and his view.® on
interpretation of the usual waves as well as a number of additional wave.s which appear in his
records. There is also a section on the pneumo-cardiogram and the esophagocardiogram. The
il!u®trations are good.

J. K. Lewis, M.D.

KLi.CTROCAftDiOGRApiiy IN PRACTICE. By .XslUon Gra\biel, .M.D., and Paul D. White, M.D.,
with the a-:®i‘.tance of Louise Wheeh r, A.M.. and Conger Williams, M.D. Second edition,
Philadelphia and London, 1946, W. B. Saunders Company, 458 page.s, 323 illustrations.
Price $7.0;).

'lilts lueful b(K)k has been expanried and mucb new materia! has been added. The original
format and plan have Ixvn retained with the presentation of the clinical information and clectro-
c-tr^ho-.tr.siihic interpretations- on one page and the clectrocarrliograms shown on the facing page.
D\ef tiftv iigures liave been adder! to this new edition and more attention is directed to the jire-
c-.cdnl chH:tr<>mr(ho4t.ain. Some coii'-ideration is given also to the more fundamental aspects of
ilectrtVMrdio-gT.qihy, New clwrts have been includeil which summarize in tabular form the
clLar,''‘teri-.tirs o! the various arrhythmias, the clectrocardiocraphic findings in various type® of
ae.tl (msuiition- secondarily aftecling the heart, ami the electrocardiographic effects
o. nviny d-ug® aisrl phvi’olcr.tirral processt--. The v.'duable and instructive si-clion of the book
t ■artam-r.- u->t ' uclre)!rardio,'ram--” i- made up entirely of new material.

076

BOOK REVIEWS

677

As in the first edition of the work, "coronary heart disease” is given as an etiological diagnosis
for many of the electrocardiographic deviations discussed. Although it is agreed that coronary
arterial disease is accountable for the majority of these abnormalities, this usage may incline
some readers, to the usually unjustified practice of making pathological diagnoses such as this
from electrocardiographic data alone in the absence of such extensive clinical information as is
available vith these cases. Doctors Graybiel and White state that they have found a lead from
the right sternal margin (precordial position 1) rareb" useful. This experience is not in accord
with that of other observ^ers who have been interested in multiple precordial leads and may
account for the lack of emphasis in this volume upon the contrast in form of the precordial electro-
cardiogram in right and left ventricular hypertrophy. The atlas system of presentation makes
for some repetition of discussion. While this may serve a useful teaching purpose, it may be dis-
advantageous when unintended inconsistencies occur. For example, in an early section of the
book, it is said that the records under consideration display both complete atrioventricular
block and bundle branch block, whereas at a later point, the writers amplify the discussion to
indicate correctly that these diagnoses cannot be made together because of uncertainty regarding
the site of the idioventricular pacemaker. The illustrations are very clear and well presented,
although Fig. 80, page 119, is inverted and reversed. The typography and paper are of good
quality.

This book should serve well as an aid in the interpretation of electrocardiograms as they are
met in general practice, the purpose for which it was written. It should be particularly valuable
in that it provides a larger number of quite typical electrocardiograms for study and review.

Francis F. Rosenbaum.

American Heart Association, Inc.

1790 Broadway at SStii Street, New York, N. Y.

Dr. Rov W. Scott
PrtsidtT.t

Dr. Howard F. West
Vicf-Prcsidrni

Dr. George R. Hekraiasn
Treasurer

Dr. Howard B. Sprague
Secrelary

BOARD OF DIRECTORS

Dr. Edgar V. Aiixs Rochester. Minn.

Dr. GRAnAM Asher Kansas City. Mo.

*De. Arue R. Barnes Rochester. Minn.

Dr. Altked Blalock Baltimore

*Dr. William H. Bunk Youngstown. Ohio

Dr. Clartnce de la CiiAPru-n. .New York City

•Dr. Tinsley R. Harrison Dallas

Dr. George R. Herr.masn Galveston

Dr. T. Duckett Jones Boston

Dr. Louis N. Katz Chicago

Dr. Samuel A. Leatke Boston

De. Gilpkrt Matouardt Chicago

•De. H. M. ?.!arvik New Haven

•Or. Kdavin P. Maa-nard, Jr Brooklyn

•De. Thomas M. McMillan Philadelphia

Dr, JoNATitAN Meakins Montreal. Can.

Dr. E. Sterling NiatoL. . . Miami

•Executive Committee.

Dr. Harold E. B. Pardee New York City

Dr. William B. Porter Richmond. Va.

•Dr. David D. Rutstein New York City

•Dr. John J. Sampson San Francisco

Dr. Roy W. Scott Cleveland

•Dr. Howard B. Sprague Boston

Dr. George F. Strong.. .Yancouver. B. C.. Can.

Dr. William D. Stroud Philadelphia

Dr. Homer F. Swift New York City

Dr. Wiu.iam P. Thompson Los Angeles

Dr. Harry E. Ungerleider. .New York City

•Dr. Howard F. West Los Angeles

Dr. Paul D. White Boston

Dr. Frank N. Wilson Ann Arbor

•Dr. Irving S. Wright New York City

Dr. Wallace M. Yater . . .Washington, D. C.

Dp.. H. M. Marvin. Acting Executive Secretary
Anna S. Wright. Ofice Secretory
Telephone, Circle S-8tXX)

T HIl .^mcrican Heart .Association is the only national organization devoted to
educational work relating to diseases of the heart. Its activities are under the
control and guidance of a Board of Directors composed of thirty-three eminent phy-
.sicians who represent cverT' portion of the country.

A central office is maintained for the coordination and distribution of important
information. From it there issues a steady stream of books, pamphlets, charts, filmsi
lantern slides, and similar educational material concerned with the recognition, pre-
vention, or treatment of diseases of the heart, which are now the leading cause of death
In the Untied States. The American Heart Journal is under the editorial super-
vision of the Association.

The Section for the Study of the Peripheral Circulation was organized in 1935
for the purpose of stimulating interest in investigation of all types of diseases of the
blood and lymph vessels and of problems concerning the circulation of blood and lymph.
.Any physician or investigator may become a member of the section after election to
the American He.irt Association and payment of dues to that organization.

The income from membership and donations provides the sole financial support
of the Association. Lack of adequate funds seriously hampers more intensive cdu-
nitional activity and the support of important investigative work.

Annual membership is $5.00. Journal membership at $11.00 includes a year's
sub'.cription to the .American He.ap,t Journal (January-December) and annual mem-
bership in the Association. The Journal alone is $10.00 per year.

Tlic .As'od.Ttion earnestly solicits your support and suggestions for its work.
Membership application blanks will be sent on request. Donations will be gratefully
m-eivtd am! promptly acknotvlcdgcd.

American Heart Journal

VoL. '32

December, 1946

No. 6

THE EXPANDED PROGRAM OF THE AMERICAN HEART ■

ASSOCIATION FOR 1947

National Heart Week, February 9, 1947

T he current activities of the American Heart Association are of national
interest to physicians as well as to layrhen who have long looked for the de-
velopment of a comprehensive public health program directed against diseases
of the heart and blood vessels — the leading cause of death in the United States.

Those familiar with its growth will recall that the American Heart Asso-
ciation was founded in 1924 to combat the growing prevalence of heart disease.
During the following two decades, the American Heart Association developed ’
professional prestige and acceptance as the only national agency devoted to
educational work relating to diseases of the heart. Organized primarily as a
professional scientific organization, the Association concerned itself largely with
the publication of the American Heart Journal, the only journal published in the
United States which limits itself to problems of the heart and blood vessels;
with the preparation of other materials for the postgraduate education of phy-
sicians; and with the establishment of standards in the field of cardiovascular
disease.

The war stimulated the development of special activities particularly with
reference to rheumatic fever. In 1944, recognizing the crucial need for a national
program to fight rheumatic fever and rheumatic heart disease, the American
Heart Association called a conference to consider the organization of a program.
The conference was attended by representatives of practically all national
voluntary health organizations and governmental agencies concerned vfith
rheumatic fever and by representatives of the Army, Navy, U. S. Public Health
Service, the Veteran’s Administration, and the Children’s Bureau.

Following this conference, the American Council on Rheumatic Fever of
the American Heart Association was formed with representatives of twelve
national medical agencies.* Today the Council is concerned with all phases
of the American Heart Association’s program which relate specifically to rheu-
matic fever. It operates administratively through the American Heart Asso-
ciation.

Earlier this year, the American Heart Association reorganized its adminis-
trative structure and broadened its objectives in order to meet the urgent need
for national action in solving the medical, social, and economic problems of heart
disease. Prominent laymen were admitted to membership on the various execu-
tive boards, and a program of interrelated membership with all local Heart
Associations was instituted. In order to preserve the scientific aspects of the
program of the American Heart Association, a Scientific Council, composed of
representatives of all scientific fields contributing to our knowledge of heart,
disease, is being formed.

♦American Academy of Pediatrics. American Association of Medical Social Workers, American
College of Phvsicians. American Heart Association, Inc., American Hospital Association, American
Medical Association, American Nurses’ Association, American Public Health Association, American
Rheumatism Association, American School Health Association. National Organization for Public
Health Nursing, and National Society for Crippled Children and Adults.

679

Tils' exft-ni JO tt'Io'ch the American Heart Astociation has expanded its ob-
lives is indicated in this condensed outline of its 1946-1047 program.! t his
niAerarn caib for the functioning of the American Heart Association as a clearing
hou-^- for ixirdiovascular activities throughout the I'nited States: for a national
mforniationa! campaign to educate the public on essential problems of heart
dit-at.'*; for postgraduate education of the medical profession, including medical
^!u(ients. in cardiac and Vviscular diseases: for provision for the application of
pabiir health techniques to control rheumatic fever and other heart diseases
througli the estahU.dimeni of standards for the many facilities needed in such
programs, the stimulation of more accurate vital statistics, and the application
I'.f epidemiologic techniques to the study of heart disease and rheumatic fever:
far tlie health education of other professional groups including social workers,
te.u'hers, school administrators, physical education instructors, school physicians,
puliiic health nurses, and public health workers: for aid to the cardiac patient
in employment: for re-evaluation of cardiac disability in life, healtli. and acci-
dent insurance: and for sponsoring and financing clinical and laboratory research.

The recent award of S.=>0,000 by the American Legion to the American Coun-
fi! on Rheumatic Fever of the American Heart Association has done much to
initiate an important approach to rheumatic fever. One-half of this amount
lias liecn allotted to (he creation of two three-year research fellowships. Twelve
thousmd five hundred dollars have gone to the establishment of a Statistician’s
Ofiice which is providing a much-needed statistical service for planning com-
munity rheumatic fever registries aii'l the preparation of satisfactory methods for
the eIas.sificaiion of deaths from heart diseases. Tlie remainder of this grant is
being spent for the fir.st of a series of medical field consultants to work directly
with communities requiring aid in setting up rheumatic fever programs.

The .'\merican Legion’s grant illustrates the need of the American Heart
.\ssociation and its affiliate, the American Council on Rheumatic Fever, for
voluJitary financial support in order to undertake the various activities outlined
in its program. Tlie 1'147' budget of the Association requires a minimum of
.^286,000 for ndminis»ration. Grants in aid for research projects call for an addi-
tional budget of $275,000. This total budget of $561,000, which has been ap-
pros’ed by the National Budget Committee, represents the minimum goal re-
quired by the American Heart Association to carry forward its program and,
at the same time, to create the basis for a national public fund-raising drive in
19-18.

To provide the nece.ssnrv public acceptance for such a drive, the American
Heart .Association is now conducting a nationwide program of public information
and education on diseases of the heart and blood vessels. The public is being
informed of the significance of high blood pressure, infections, overweight, rheu-
matic fever, and other factors contributing to various types of heart disease.

Plans have been developed for the obser\'ance of National Heart Week
which i<^ to be inaugurated Feb. 9, 1947. During this week, the importance of
care, treatment, prevention, and study of circulatory problems will be empha-
ssj'ed, and the public will be reminded that heart disease is om first national health
problem and that it can be combatted only with the ‘‘ullest cooperation of the
scienfiiic v,'orker. the specialist in heart and peripheral vascular diseases, the
practicing physician, and the indivitlual citizen and his community.

_ It is the plan of the American Heart Association to carry out selective fund-
rairing activities during National Heart Week and during the remainder of the
year in cnoporation with local Heart Associations Avhere thej'^ e.xist. As the public
brciiiucs informed and aware of the significance of heart disease as a serious
pwi.ir health problem, the stage will be set for a comprehensive nationwide
apr5;£jnr rontribution.=i in 194$.

«Tl i^<r* l»,t<
<<• Arfi^desr}

in ^'-curlRr o irorc itotallrd of tliis prow-iin art" rctiUMna to tirtto

Inc, 17PO nmafl«a>. N>«- Yort., .V, Y.

Original Communications

THE ESOPHAGEAL ELECTROCARDIOGRAM IN ARRHYTHMIAS

AND TACHYCARDIAS

Scott Butterworth, M.D., and Charles A. Poindexter, M.D.

New York, N. Y.

^■^HE technique of taking electrocardiographic tracings with an electrode in the
esophagus is a procedure which dates from the early days of electrocardio-
graphic research.” Special studies^"’ have demonstrated the use of these leads
in a variety of conditions. The present paper deals only with the value of the
esophageal electrocardiogram in certain arrhythmias and tachycardias, although
it is also of recognized value in the study of the electrical field of the heart and
in the diagnosis of posterior myocardial infarction.

There is nothing new or unique in this work, but for some time we have been
impressed that certain electrocardiograms are difficult or impossible of accurate
interpretation without absolute knowledge of the position of the P wave. All
too often, both in published and unpublished reports, the interpretation has been
based upon theory rather than on demonstrated fact, and it has seemed to us.
that in selected cases valuable additional information could be obtained by the
vise of the esophageal lead. For this reason, it has been our practice to take
esophageal electrocardiograms in all cases where the P waves were not distinctly
visible in any of the leads from the surface of the body. Occasionally the P
waves may be augmented by paired leads from the right sternal border, but the
most satisfactory lead for demonstration of P waves is derived from an electrode in
the esophagus adjacent to the auricles. An electrode in this area produces a
pattern approaching that obtained by a direct lead from the surface of the auricle.

Esophageal electrodes may be simple, having a single terminal at the tip
of the tube, or they may be complex, having numerous terminals located at in-
tervals near the tip. For all practical purposes, a single terminal is very satis-
factory, and such a device may be constructed with a few minutes of labor. An
ordinary Rehfuss stomach tube is cut to a length of about 70 centimeters. A
small bolt which will conveniently fit the diameter of the tube is soldered to a
vfine copper wire (about No. 34). A globule of solder is attached to the head of
the bolt to provide a round, smooth tip .which acts as the contact with the wall
of the esophagus. The wire is then inserted through the tube and connected to a
terminal at the opposite end so that the wire is fairly taut in the tube. ,We
have found that a. terminal from the base of an old radio tube is very useful for
this purpose. The tube is then marked in centimeters from the tip to the 55 cm.

' Prom the Division of Cardiology, Department of Medicine, New York Post-Graduate Medical
School and Hospital, Columbia University.

Received for publication April 30, 1946.

682

AMERrCAN HEART JOURNAL

level with black lacquer. Care must be taken in cleaning the tube after use to
avoid stretching the tube, for this may break the fine wire or one of the connec-
tions.

Tlie technique of inserting the tube is exactly the same as for any stomach
lube, ^^’e generally insert the tip through a nostril with the patient in the
sitting position and push it into the esophagus during the act of deglutition as
the patient drinks water. Most patients tolerate this procedure well and it is
only occasionally necessary to anesthetize the pharynx. A small portion of
electrode paste is rubbed on the tip just before insertion. After the tube is
inserted to the 55 cm. level, the patient is placed in a supine position for the
recording of the electrocardiogram. The esophageal lead can be paired with any
other lead but we commonly use the left leg or preferably the indifferent electrode
of Wilson.

Occasionally there is poor electrical contact with the esophagus after the
lube is in place: this can often be improved by having the patient drink some warm
s'lline solution. Another difficulty which produces artefacts in the record is
.sliding of the electrode on the mucous membrane of the esophagus with each beat
of the heart. This produces very bizarre complexes but can usually be obviated
by shifting the position of the electrode slightly.

At the 55 cm. level the tip of the lube is usually in the stomach. A record
is taken at this level and the tube is then withdrawn in increments of 2.0 or 2.5
cm. to the 50 cm. level, which usually places the lip above the heart. Levels
from 55 to 40 cm. are usually in close proximity to the diaphragmatic surface
of the heart and accentuate the ventricular potentials, while those from the
40 to the 50 cm. levels usuall.v overlie the auricles and accentuate the auricular
potentials. At the lower levels one often encounters difficulty in keeping 'the
string in the field due to re.spiratory movement of the diaphragm. This can usu-
ally he controlled by instructing the patient to suspend respiration temporarily
at the end of a normal e.vpiralion. The amplifying types of electrocardiographic
machine.^ are somewhat easier to use in that the beam balances and stays in the
field more easily, lutl ail instruments are satisfactory and we have made many
records on both string and amplifying instruments.

As a general rule, the following types of mechanisms offer difficulty in inter-
pretation and may be inaccurately diagnosed due to inability to identify the P
wave definitely:

t. MUftrc)'-ardiot;r.iin> ;n which the P wave is ‘-upfrimposcci on tfie
QKS coniplt'\ or llu- T wave.

2 Elect ricar(!io;<rnnis in which the voltatre of thi* P uave is too low to
pi-rrmt po-itive identiheation,

,t. I .Tclivcartii,! of tit}n*r -uprawntricwlar or ventricular origin in which
P waves cannot l>e ('elinilely identified.

The fi.)Howinc examples are presented to illustrate these points.

I

H.LUSTKATIVE EI.ECTHtX-AROIOGKAMS

The firsi case (Fig. 1) js; an illustration of a P wave buried in the T wave,
jthageal lead*^ .are not u-ually necessary in this type of case for the P-R

SI?!:. .:

,7Ijtfc«S fc*

Fig. 1. — The standard leads in this case do not sho'sv definite P waves, but from the auricular level
of the esophagus the P waves are seen to fall on the summit of the T waves. (The first three complexes
of the lead from the auricular level of the esophasgus (E*) have been retouched to improve reproduction,
and the P waves are marked.)

p-jg, 2. — Electrocardiogram illustrating extremely low voltage of the P waves in the standard
leads. The Ea lead clearly shows the P waves. There is complete dissociation between the auricles
and ventricles.

Fig. 3 . — TIiP j.taii(liir<l iKiUs rpvoal jio
(li'flnilo F wiivos aiifl an irregular rhythm.
The •suppti.'sitlon would be that one is deal-
ing with rapid auricular fll>riIIation. al-
though e.vperlenced electrocardiographers
mlclit su.spi-ct auricular tlutter. The Ea
lead cletirly demonstrates that the mech-
anism l.s -juricular flutter with ttirying
Idock. The K waves are marUotl at the
top and file I> waves at the bottom of the
Ea n'cord.

Fig. 4 .~ No I’ waves are apparent in
tiie .standard leads, luji the Ka lead shows
a notching of tlte descending limb of H
wave whieli reprr-s-eni.s' the P wave. For
eomparlson. a smell portion of a traeing
from therame level after return to normal
rhjtlim is Included It ran be seen that
tb*' P wave ts now In Its normal position
In from of the qus and the notching of
the drscernlitig iimb of the .s: wave lias
dlsappe.-jrtsl. ThlsestahH.sInsja diagnosis
of nodal tacliy<3irdla.

BUTTERWORTH AND POINDEXTER: ESOPHAGEAL ELECTROCARDIOGRAM 685

interval will vary from day to day, or accelerating the pulse by administration
of atropine or by exercise will shift the P wave from the T wave so that it becomes
visible. In this particular case the P-R interval returned to normal over a period
of several weeks.

A.

B.

pjg 5 _ The leads under B show a marked ventricular conduction defect (RBBB) which was

present prior to the tachycardia shown under A. Under these circumstances it seemed impossible to
decide if this was a case of supraventricular tachycardia with a ventricular conduction defect or a ven-
tricular tachycardia. The E* lead definitely astablished the diagnosis of ventricular tachycardia.
The small blocks at the top of the record represent the QRS complexes and the vertical lines, the P
. waves showing an independent auricular rhythm much slower than that of the ventricles. (The Ea
lead. is an exact tracing of the electrocardiogram and was made solely to improve reproduction.)

The electrocardiogram in Fig. 2 illustrates the type of case in which the
voltage of the P wave is too low. to make identification positive. There are sug-
gestive P waves in Leads II and III, but they are not definite enough to be con-
vincing. From the auricular level of the esophagus, however, the P waves stand
out well and it is clearly seen that the auricles have an independent rhythm
slower than that of the ventricles.

686

AMERICAN HEART JOURNAL

In Fig. 3 the rate is rapid and irregular, although there are sequences which
seem fairly regular. No definite P waves can be identified, and the most obvious
diagnosis would be rapid auricular fibrillation although experienced electro-
airdiographers would suspect flutter. The esophageal lead at the auricular level
(Ea) reveals definite flutter waves which are perfectly regular at a rate of 300 per
minute in contrast to the ventricular rate of about 140.

Kttr. r., — Tl)is J>; thf- oIi-ciroc.nniioKmm of a -M-yoar-old man duriiiK an opUodc of tachyc.-irdla which
occurrceS one wi-ch after an acute anterior inyocardla! infarction. Tlio csoplmjtcal clcctrocardloprarn
chows \cry larRo P vtavee at a slotvor rliyttini than tliat of tlic ventricles.

Fi.g. 4 illustrates a case of paroxysmal tachycardia which was assumed to
he nodal rhythm because no P waves could be identified in the standard leads.
The esophageal lead revealed the P wave on the descending limb of the S wave.
A tracing from the same level after return to normal sinus rhythm is also included
and the P wave.« are clearly present before each QRS complex, and the notching
ttn the downstroke of the $ wa\'e has disappeared although the remainder of the
QRS and the T wa\'c.s hnvt* not been altered. This proves the original assump-
tioj! of nodal rhythm.

t-'ig. 5 shovv.s electrocardiograms of a 52-year-old man who was subject to
frequent attacks of paroxy,smal tachycardia. It is of interest that electro-
cartliintrams taken fluring periodsof normal rhythm (B) revealed a marked intra-

BUTTERWORTH AND. POINDEXTER : ESOPHAGEAL ELECTROCARDIOGRAM . 687

ventricular conduction disturbance. When we succeeded in obtaining a record
during an episode of tachycardia {A), it had the appearance of a ventricular
tachycardia, but because of the previous conduction disturbance, it was not clear
whether this was a true ventricular tachycardia or a supraventricular tachy-
cardia in the presence of the previously demonstrated ventricular conduction dis-
turbance. An esophageal electrocardiogram was therefore recorded, an actual
tracing of which is shown at the bottom of Fig. 5. (A tracing is used rather than
the original record solely to improve reproduction.) 'The small blocks at the top
of the tracing represent QRS complexes and the vertical lines represent P waves.
This record clearly shows a slow auricular rate independent of the ventricular
rate and establishes the. diagnosis of ventricular tachycardia.

The last illustration (Fig. 6) shows the electrocardiogram taken on a 44-
year-old man during an episode of sudden tachycardia which occurred one week
after an acute anterior myocardial infarction. The standard leads were not con-
sidered sufficiently diagnostic to differentiate between auricular tachycardia,
nodal tachycardia, auricular flutter, and ventricular tachycardia, so an esophageal
electrocardiogram was taken. This procedure did not upset the patient in
any way. The Ea lead shows very large P waves which overshadow the QRS
complexes. These waves were at a slower rate and independent of the ventricular
complexes, showing that the origin of the tachycardia was below the auricles.
The patient was treated with large doses of quinidine sulfate by mouth and
the abnormal rhythm was converted to a normal sinus rhythm within a few
hours. Further convalescence was uneventful. Leads from the ventricular level
of the esophagus (not illustrated) revealed a characteristic depression of the
S-T segments which is commonly seen with anterior myocardial infarction.

DISCUSSION

Our purpose in presenting this material is to emphasize the value of the
esophageal electrocardiogram in making accurate diagnosis in certain cases of
tachycardia and arrhythmia. We feel this procedure has, in general, been neg-
lected. ' The records are easy to take and simple to interpret after a short period
of orientation.

Accurate interpretation is important not only to further our knowledge of
electrocardiograph 3 ^ and to prevent inaccurate diagnosis from infiltrating the
literature, but also because of the necessity of having an accurate diagnosis on
which to base proper therapy.

SUMMARY

1. Several electrocardiograms are reproduced, illustrating the value of the
esophageal electrocardiogram in accurately diagnosing certain types of arrhythmia
:and tachycardia.

2. A plea has been made for more frequent use of the esophageal elec-
trocardiogram in selected cases.

AMI-KICAX HKART JOURNAL

REFERENCES

Lu lx'f-on. Abraham, and Liberpon, Frank: An Internal Electrocardiographic Lead, Proc.
SfK-. E:<rwr. Biol. & Med. 31 : 441, 1934.

p.rov, n W'. Ihirst: A Stiid\’ of the Esophagc.al Lead in Clinical Electrocardiography, Am.
Hi.art J. 12: 1, .307, i936.

J.: The Esophageal Elcctrooardiograni in Coronary Thrombosis, J. Clin. Inyesti-
gation Ifi: 495, 1939.

\vbocr. J., and Hamilton, J. G. M.: Oesophageal Electrocardiograms in Auricular Fibrilla-
tion. Brit. Heart J. 2; 263, 1940.

Wolferth, Charles C., Bcllett, Samuel. Livecey, Mary M., and Murphy, Franklin D.: Nega-
tiye Displacement of the RS-T .Segment in the Electrocardiogram and Its Relationship
to Positiye Displacement; an Experimental Study, .Am. Heart J. 29: 220, 1945.
RoM-nbaum. Francis F,. Hecht, Hans H., Wilson. Frank N., and Johnston, Franklin D.:
The Potential Variations of the Thorax and the Esoplrngus in Anomalous Atrioven-
tricular Excitation (WoKT-Pnrkinson- White Syndrome), -Am. Heart J. 29; 281, 1945.
Lulsada, Aldo: A Review of Advances in the Stutlv of Auricular Disorders, J, Lab. <St CUn.
Med. 2.3: 1146, 1940.

ANOXEMIA AND EXERCISE TESTS IN THE DIAGNOSIS OF
• . CORONARY DISEASE

Gunnar Biorck, M.D.

Stockholm, Sweden

QINCE the usefulness of functional tests in the diagnosis of coronary heart
disease still seems to be under discussion, this paper attempts to answer
some of the questions pertaining to this matter from a clinical point of view.

According to Blumgart and co-workers,^ coronary heart disease comprises
angina pectoris, coronary failure, and acute myocardial infarction. In the last
two conditions the patient is seriously ill and np consideration will be given to
the aid that functional tests afford in making the diagnosis. The application of
improved diagnostic measures will be limited to angina pectoris. Does the
clinical management of angina pectoris require methods of study other than
the history, physical examination, electrocardiogram, roentgenogram, and ordi-
nary laboratory tests? Some experienced clinicians perhaps would answer in the
negative. They feel sure that the diagnosis is best made from the history and
usual clinical examination. Others feel a need for more objective methods in
dealing with a condition which is subjective in its manifestations.

\yhite2 has stated that 25 per cent of his patients with a history of angina
do not show any abnormality of the heart by the usual methods of examination.
In about 150 of our patients with suspected angina (perhaps a somewhat less
well-defined group than White’s) the diagnosis of this condition was reasonably
certain in only one-sixth ; of the others, coronary artery disease was strongly sus-
pected in t^vo-thirds, and in one-sixth the diagnosis was in doubt. With the
increasing incidence of cardiac neuroses, social and military benefits, and, perhaps,
compulsory health insurance, the needs for improved objective diagnostic meas-
ures are definite. For experimental purposes and for studies before and after
surgical procedures on the heart they are also useful beyond question.

For which types of patients are tests especially desirable? There are three
groups to be dealt with: (1) patients with some sort of disorder in the chest,
very slightly suggestive of angina ; (2) patients whose symptoms resemble those
of angina, but whose chest pain is mild or otherwise atypical; and (3) patients
with clear-cut angina, with or without previous myocardial infarction.

The main purpose of "coronary” tests is to reveal a latent coronary insuffi-
ciency. This means that tests are indicated in suspected cases without a "cor-
onary” electrocardiogram at rest. It is also likely that additional strain brought
about by tests, even in patients with a coronary electrocardiogram at rest, will
give some evidence of the remaining so-called "coronary reserve.”

Even if one admits that in the first group of patients with slightly suspected
angina the use of "coronary” tests can be confined to those in whom no other

From the Sabbatsb erg’s Hospital.

Read before the Harvard Medical Society, Boston, Feb. 12, 1946.

Received for publication May 9, 194.5.

689

690

AMERICAN HEART JOURNAL

positive diagnosis could be obtained and, also, that in the .third group, the
members of which give a very convindng historj^ of angina and usually some posi-
tive findings on clinical examination, the use of the tests is of limited value,
there still remains the large second group of patients with moderately suspected
angina, many of whom will not show evidence of coronary insufficiency in the
electrooirdiogram at rest. This is the group in which tests, from a diagnostic
standpoint, are most desirable. With regard to the determination of the "cor-
onary reserve” in patients with a coronary electrocardiogram at rest, it is too
early to evaluate its prognostic significance. Sufficient statistics are as yet not
available. As long as that problem is not solved, it is reasonable to continue to
perform the tests also in this group of patients for later follow-up studies.

Assuming that tests are desirable, how should they be planned.? Anginal
pain and its equivalents arc supposed to represent, clinically, a local ischemia
of the myocardium, as do the electrocardiographic findings usuallj'^ mentioned
as evidence of coronary insufficienc 3 % The test should, therefore, provoke
pathologic changes in the coronary circulation and cause a relative dispro-
portion between the demands of the myocardium for oxygenation and the
supply of oxyhemoglobin through the coronary blood flow, thus eliciting either
anginal pain or typical electrocardiognaphic changes, or both.

There are at least three ways to provoke such conditions and responses.
One can reduce the oxygen saturation of the blood, either by giving a patient
a gas mixture which is deficient in oxygen or by using a low-pressure chamber;
one can exercise the patient, which increases the cardiac demand for oxygen
without reducing the supply; or one can increase the work of the heart by adre-
nalin, whicli is a very dangerous method that we have not used. Apart from
other considerations, the first method, the ano.xemia test, is probablj' to be pre-
ferred for the study of the coronary circulation per se, and the second one, the
exercise test, for the estimation of its capacity in the more natural environment
of the whole system of reflexes, body metabolism, and hormonal activity

In the anoxemia test (in Sweden we prefer to call it the hypoxemia test)
wc use, according to the technique devised by LeAy and associates,^ 10 per cent
oxj’gen and 90 per cent nitrogen breathed for twenty minutes, or less in case
definite anginal pain or other unpleasant reactions should develop. Immedi-
ately after finishing the test, the patient is allowed to breathe 100 per cent oxygen
for at least five minutes. We have also felt it wise, for the sake of comparison,
to use the original criteria of Levy and co-workers®^ in the interpretation of the
electrocardiographic findings (Table I). In a later paper®*^ they discarded
their fourth criterion.

There are at least two remarks to be made about the discrepancy between
the theory and the reality of this test. The first concerns the oxygen saturation
of the blood. Beciuse of different types of breathing during the period of
anoxemia, even in case of good pulmonary function, the oxygen saturation of the
arterkil bhwd. and probably also the carbon dioxide content and the pH of the
iiloorl, will differ from patient to patient. The same oxygen percentage in the
inspired air will mean, to some extent, different things to different patients.

BIORCK; ANOXEMIA AND EXERCISE TESTS IN CORONARY DIAGNOSIS 691

Table I. Criteria

Anoxemia , — ^The test is positive if any one of the following is found:

1.. The arithmetic sum of the S-T deviations in Leads I, II, III, and IV F is greater by
3 mm. or more than in the control.

2. There is partial or complete reversal of the direction of the T wave in Lead I, accom-
panied by an S-T deviation of 1 mm. or more in this lead.

3. There is complete reversal of the direction of the T wave in Lead IV F, regardless of any
S-T deviation in this lead.

4. There is partial reversal of the direction of the T wave in Lead IV F, accompanied by
an S-T deviation of 1 mm. or more in this lead.

Exercise (New, “rigid” set of criteria)*. — The test is positive if:

1. The S-T depressions in Leads I, II, and III exceed together 2 mm.

2. Ti or T 2 are inverted.

3. Ti is diphasic and S-Ti is depressed at least 1 mm.

4. Anj- single S-T depression is 1.5 mm. or more.

*These are to be regarded only as an attempt to establish better criteria than we formerly had.
They may be changed following further experience and later follow-up studies.

Perhaps this objection can be met by using the Millikan oximeter for serial
readings. If it works well, it is possible that the test, in the future, can be stand-
ardized according to the oxygen saturation of the blood rather than by the oxygen
percentage in the inspired air.

The other objection to be discussed concerns the interpretation of the so-
called coronary changes that appear in the electrocardiogram. There is still
(perhaps now more than at any time) much obscurity about the underlying
mechanism both with regard to the production of pain and with regard to the
electrocardiographic signs of coronary insufficiency. The number of causal
explanations is still increasing, and the importance of functional influences
is more and more stressed. Such criticism is correct. It is obvious that further
electrocardiographic, biochemical, and physiologic studies are greatly needed.
■But, in my opinion, this criticism should not retard attempts to gain further in-
formation about the reactions of the heart with diseased coronary arteries.-
It may, however, dispose us to a certain caution in our interpretation of the tests.

With this in mind, how does the anoxemia test work out clinically? In
Table II are shown the results with anoxemia tests which have been published
by Larsen (IQSS),"* by Levy and associates (1941) and by Pruitt, Burchell,
and Barnes (1945),® together with our own material which has been collected
since 1942, when the test was introduced in Sweden by Dr. Gustav Nylin. In
1944, I had the opportunity to make the first survey of the test’s results.® The
report of Burnett, Nims, and Josephson' is not included since the use of a
different oxygen tension of gas mixture prevents a comparison of their results
with burs.

Table II is made up with regard to the previously mentioned three groups
of patients with suspected angina, and the published statistics are classified
according to these groups. Contrary to the procedure of the others, my clinical
classification has been made without knowing the form of the electrocardiogram
at rest.

692

AMERICAN HEART JOURNAL

IT. Comparison- Bet^veen Percentage of Positive Anoxemia Tests in Three IVIain
Ceintcal Groups, Compiled From Reports of Various Investjgators

1

i

IXVL.'.TIGATOR i

GROUP I
NORMALS AND
SLIGHTLY SUSPECTED
“coronary” CASES

1 . _ _

GROUP n
MODERATELY
SUSPECTED
“coronary” CASES

GROUP III
PROBABLE OR
CERTAIN

“coronary” oases

1

xo. 1

vnil CENT '

1

NO.

PER CENT

NO.

PER CENT

I.Arscri (1038)' (9% 0,)

1

28

0

1

i

26

i

15

17

77

Lew (!')4!y'-

115

0

33

18

22

31*

1

1

i

1

73

55t

I’ruitt. Burct’cll, and

!

Barnes (I045)‘

89

1.1

108

19.5

92

53

1

lUorcL (1046)®

149

1 2.7J

131

[ 19.8

46

30

20

40§

'\o an 'inal pain.

I Anplnal pain.

P'onr positive tests In cases with doflnite pulmonary disease or other types of heart disease hut
t'o ■ roronary” symptoms.

JAhiiornial ECG at rest,

'riiere seem to be four conclusions to be drawn from Table II: (1) There
Alt' no positive tests in the group of normal subjects or patients with slightly
‘-iispected angina, if evidence of other cardiac disease, definite respiratory im-
pairment, or severe anemia is ruled out. (2) One will have to e.xpect about 20
per cent positive tests in the moderately suspected group. This figure is sur-
prisingly constant throughout the three series of statistics which are based upon
identical technique and criteria. In my material the figure is 18 per cent in 100
patients without a coronarj' electrocardiogram at rest, and 27 per cent in thirty-
one with a coronary electrocardiogram at rest; in the whole group, it is 19.8
per cent. (3) Between 30 and 50 per cent of the patients with probable or cer-
tain coronar}- disease will show a positive test. (4) The conclusion follows that
a negative test does not e.xcludo the e.xistence of coronart'^ disease. Since Table II
is liased upon a study of 939 cases it should have statistical significance.

What is the correlation between the outcome of the test and the findings
at autopsy? Although functional influences may be of some importance in the
production of the anginal syndrome, we must, for the verification of our diagnosis,
rely on the anatomic findings. Table III shows a comparison between the re-
suU.s of ihe anoxemia tests and the post-mortem findings, or, when no post-
mortem study was performed, tJte type of death: an acute death, which probably
ro>uUcd from myocardial infarction, ventricular fibrillation, or asystole; or,
in contrast, death from progressive congestive failure or from intercurrent
disease. The figure.s are collected from Lcaw's publioitions and from our ma-
tena . 1 he senes thus studied is not as yet verj- large, but the results are rather

BIORCK: ANOXEMIA AND EXERCISE TESTS IN CORONARY DIAGNOSIS 693

Table III. Correlation Between Results of Anoxemia Tests and Condition of Coronary

Vessels at Autopsy or Type of De.\th

POST-MORTEM FINDINGS

MARKED

CORON.ARY

SCLEROSIS

SLIGHT OR

NO CORONARY
SCLEROSIS

levy’'

BIORCK®

Positive tests

1

1

—

—

Negative tests

Abnormal ECG at rest

2

2

—

- 1

Normal ECG at rest

—

—

1

2 )

Negative tests with anginal
pain

-

NO post-mortem

TYPE OF DEATH

ACUTE DEATH

CONGESTIVE

FAILURE

LEVY’'

BIORCK®

i

LEVY^^'

BIORCK

5

1

—

—

1

*1

2

J

3

2

4

1?

G

It will be of great interest to follow up a larger autopsy series. For our
part, we have also separated a group of "doubtful” cases, with electrocardiograms
definitely changed, but not sufficiently so to fit in with Levy’s rather rigid criteria;
we intend to follow this group also in order to estimate the significance of such
slighter changes.

It is the general experience that in some cases the test can change from
positive to negative after an interval of time has elapsed. This may be ascribed,
in part, to so-called functional influences, but it may also be the expression of
substantial changes in the coronary circulation. The development of coronary
sclerosis is not a constantly progressive process but one which occurs stepwise.
A sudden narrowing or occlusion may produce a state of impending infarction,
accidentally disclosed by a test; at the time of the next test a sufficient collateral ,
circulation niay have been established to result in a negative test. It is possible
that a stable positive test is a more favorable sign than a changing one, for the
latter may indicate either an active sclerotic process or a functional instability,
both equally undesirable.

In this connection it is proper to discuss the hazard of the test. Table IV -
shows the unpleasant reactions which have been reported. . In addition to these
figures, there may be mentioned two other cases of pulmonary edema in Levy’s-
earliest cases, and two vasovagal reactions which occurred in our clinic in 1945.
The vasovagal reactions are probably partly unavoidable; they are usually not
accompanied by coronary tracings, and they are, with proper observation and
treatment, harmless. Psychogenic reactions are likewise hard to avoid because
some of these cases cannot be valuated without the test. If the test is performed
on proper indications, if the technique is Avell controlled, and if the observation
of the patient is careful, trouble should not occur.

694

AMERICAN HEART JOURNAL

Table IV. U-SPleasant Reactions During Anoxemia Test

1

j

1

1

j

levy’®

levy’'

I'Ruirr,
BERCnELL,
AND BARNES’

BIORCK’

Total number of patients

262

137

289

326

Re.ictions

1

Vasovagal syncope

12 (11)*

i S (6)

9

1

Unconsciousness

2 (1)

3

Convulsions

1

Cardiac arrhvthmia

3

?

Pulmonary edema

1

Severe anxiety; hysteria

1

5 (3)

1

1

I

*I'iRUrcs In brackets Indicate number of patients with that reaction.

In some cases the test brings about severe anginal pain without marked
dianges in the electrocardiogram at the time it is interrupted. If there is real
anginal pain, which is, in some cases, hard to judge objectively, Levy's and also
our experience is that coronary' disease is very probable. It is possible that an
ischemic area, not located near either the endocardium or the epicardium, can
be responsible for this circumstance. It is also possible that cardiac pain can arise
in the trails of the coronary vessels. As the ano.xemia test, as well as other tests,
should be regarded only as an aid to the clinical diagnosis, we probably still
should limit the criteria of a positive test to objective findings, although we
may feel quite free to evaluate the provocation of pain for what it may be worth
in our clinical conception of the patients’ stale.

Finally, a few words about exercise tests. In the United Stales these tests
ha\'c been studied and used by Master® and Riseman and co-workers.® These
investigators have used a two-step test; Master has used standardized work
while Riseman and co-workers have continued exercise until pain appeared.
In performing tlie exercise test, we have used Nylin’s staircase, which is also used
for functional studies of the oxygen consumption. The work is generally stand-
ardized to 5 rounds at a rate of 160 steps per minute, which most patients whom
we expose to this test are able to perform without pathologic increase of their
oxygen debt. Our opinion is that exercise tests should be standardized if the
result'^ are to be judged by the electrocardiograms. If the patients arc allowed
to work until they experience pain (which is a subjective limit), it is more logical
to judge result-s from the amount of work performed rather than from changes in
the cloctrociirdiograms. The time between the completion of the work and the
taking of the electrocardiograms is of importance. We have had the privilege
of working with Elmqvist’s electrocardiographic instrument, which simultaneously
roo-irds five le.ids <m the same piece of photographic paper.

Bec.iu?e of the differences in technique, it is hard to compare our results
with those obtained by Americtin workers. There is also the question of criteria.
None of those who have written on exercise tests has used the same criteria. It is
Gur exjjcrienre that, in the case of e.xcrcise tests, much of their usefulness depends

BIORCK; ANOXEMIA AND EXERCISE TESTS IN CORONARY DIAGNOSIS 695

upon the criteria applied. Formerly, we used very liberal criteria for positive
tests. Since we found that about 25 per cent of the positive tests were obtained
in those in whom coronary artery disease was not suspected (Group I of Table V),
we now apply more rigid criteria which are very similar to those employed
in the anoxemia test. Table V shows a comparison, in a series of 178 patients,
of the results of the anoxemia test with those of the exercise test, the latter judged
by means of both our old and our new criteria. Of 178 patients tested, 154
gave a negative result with both tests. In twenty-nine, the anoxemia tests
showed a greater number of positive results than did the exercise test; in four-
teen, the exercise test gave the greater number of positive results. The con-
clusion, therefore, seems justified that these tests should be used side by side
in order to give a more comprehensive view of the condition. Having used both
tests, we are of the opinion that the}'- are about equally safe in the average patient,
that the exercise test is perhaps a little simpler to perform, and that the anoxemia
test probably gives more useful information than does the exercise test. Master
and associates^® have recently compared the effects of their two-step test with the
effects of the anoxemia test, done by the Levy method, in 117 persons. They
found that both tests gave similar results. They have, however, regarded the
exercise test as positive if any S-T segment was de^dated more than 0.5 mm.
or if the T wave became inverted in any lead. These criteria are, in our ex-
perience, far too liberal. The question is, after all, not to obtain the largest possi-
ble number of positive tests but to obtain positive tests which, with certainty,
correspond' to the physiopathologic condition for which the test is intended.

Table V’. Comparison Between Anoxemia and Exercise Tests

GROUP

anoxemia

EXERCISE

POSITIVE

DOUBTFUL

OLD CRITERIA

NEW CRITERIA

POSITIVE

DOUBTFUL

POSITIVE

DOUBTFUL

I. Without suspected

1

coronary disease

1

4

6

5

2

4

II. With suspected

coronary disease

11

/

12

2

7

3

III. With probable or

certain coronary

disease

7

7

6

3

5

1

19

18

24

■ 10

' 14

8

37

34

22

As a general conclusion concerning the usefulness of these tests, the following
may be said. Because they require technical equipment, a careful general ex-
amination of the patient with regard to indications and contraindications, and a
certain experience with regard to their interpretation, and also because they

6^)6

AMERICAN' HEART JOURNAL

involve a plight chance of unpleasant and perhaps alarming reactions, they are
not to be recommended for general use. Where possible, it is preferable to refer
omdidates for the test to a special heart service. In heart clinics and laboratories
where e.xperimental studies concerning “coronary” problems are carried out,
these tests should be used. The first series of cases may be disappointing; that
was our first impression. But onh' sufficient statistics can give the proper answer.

REFERENCES

1. Blumgart, H. I... Schesinger, M. J., and ZoU, P. M.: Angina Pectoris, Ccronarj’ Failure

and Acute Myocardial Infarction: The Role of Coronar\’ Occlusions and Collateral
Circulation, J.A.M.A. 116: 91, 1941.

2. White. P. D.: Heart Disease, ed. 3, New York, 1944, The Macmillan Co.

3. a. Le^Wi F- b-. Bruenn, H. G., and Russell, N. G., Jr.: The Use of Electrocardiographic

Changes Caused bv Induced Anoxemia as a Test for Coronarv insufficienev. Am. J.
M. .Sc. 197; 241, 1939.

b. Levy, R. L., Williams, N. Is.. Bruenn, H. G., and Carr, H. A.: The "Anoxemia Test"

in the Diagnosis of Coronary Insufficiency, Am. Heart J. 21: 634, 1941.

c. Levy, R. L., Patterson, J. E.. Clark, T. W., and Bruenn, H.G.: The "Anoxemia Test”

as an Index of the Coronary Reserve, J.A.M.A. 117: 2113, 1941.

d. Patterson, J. E„ Clark, T. W., and Levy, R. L.: A Comparison of Electrocardiographic

Changes Observed During the "Anoxemia Test" on Normal Persons and on Patients
With Coronary Sclerosis, Am. Heart J. 23: 837, 1942.

4. Larsen. K. H.: Om Forandringcr I Elektrokarkiogrammet Hos Sunde Og Syge Under

Experimental Iltmangcl, Copenhagen, 1938, Ejnar Munksgaards Forlag.

3. Pruitt, R. D., Burchcll, H. B., and Barnes, A. R.: The Anoxia Test in the Diagnosis of
Coronary Insufficiency: A Study of 289 Cases, J.A.M.A. 128: 839, 1945.

6. Bibrck, Gunnar: Hvpoxaemia Tests in Coronary Disease, Brit. Heart J. 8: 17, 1946.

7. Burnett, C. T., Nims, M. G., and josephson, C. J.: The Induced Anoxemia Test: A

Study by .Age Groups, .Am. Heart J. 23; 306, 1942.

5. i»fa£tcr, A. M.: The Two-Step Test of Myocardial Function, ,Am. Heart J. 10: 495, 1935.

9. Riseman. J. E. F., Waller, J. A'., and Brown, M. G.: TJic Electrocardiogram During At-

t.icks of Angina Pectoris: Its Characteristics and Diagnostic Significance, Am.
Heart J. 19; 683, 1940.

10. Master, A. M., Nuzic. S.,^ Brown, R. C., and Parker, R. C., Jr.: The Electrocardiogram

and the "Two-Step" Exercise: A Tc.st of Cardiac Function and Coronary Insuffi-
ciency, .Am. J. M. Sc. 207: 435, 1944.

PLASMA CONCENTRATIONS OF QUINIDINE WITH PARTICULAR
REFERENCE TO THERAPEUTICALLY EFFECTIVE LEVELS
IN TWO CASES OF PAROXYSMAL NODAL
TACHYCARDIA

Allen F. Delevett, M.D.,* and Charles A. Poindexter, M.D.f

New York, N. Y.

TN THE past, methods for the estimation of cinchona alkaloids in biologic
fluids and tissue were technically difficult and relatively insensitive.^"® Re-
cently, however, Brodie and co-workers have reported new methods, based on
colorimetry, Avhich obviate these objections.'*’®

The purpose of this paper is to report (1) plasma concentrations of quinidine
in nineteen patients after a single oral dose of 1.0 Gm. of quinidine sulfate and
(2) the therapeutic range of plasma concentration of quinidine in two cases of
paroxysmal nodal tachycardia.

METHODS

The colorimetric method developed by Brodie® was used for the estimation of
plasma quinidine concentrations in this study. This method involves the extrac-
tion of the alkaloid from alkalinized plasma by means of ethylene dichloride.
Acid degeneration products, presumably phenolic in character, are then removed
from the organic phase by means of an alkalinized alcoholic wash. Next the
ethylene dichloride and contained alkaloid are shaken with methyl orange.
The result of this step is the formation of a colored compound of the alkaloid
and the dye. Measurement of the optical density of this compound is then made
in the Evelyn photoelectric colorimeter against suitably prepared standards.
With each set of plasma determinations, one or more recoveries were run, of
which the majority fell within 90 to 100 per cent.

Nineteen adult patients (nine men and ten women, whose ages ranged from
20 to 60 years) were given a single dose of 1.0 Gm. of quinidine sulfate orally.
These patients were selected so as to exclude obvious gastrointestinal, liver, and
renal disease, thus minimizing possible interference with the normal processes
of absorption, localization, degradation, and excretion of the alkaloid. All of
the patients were confined to bed during the test. Sixteen of them ate regular
meals. Of these, the majority received the 1.0 Gm. dose one to one and one-half
hours before breakfast, while the others received the quinidine several hours after
breakfast or after the noon meal. The remaining three patients of the nineteen
were fasting for the eight hours preceding and the eight hours following the drug.

Blood specimens were collected in most instances every fifteen minutes for
the fiist hour after the oral dose of the drug, and then at two, three, four, six,

. Received for publication April 29, 1946.

♦Oliver Rea Eellov in Cardiology, New York Post-Graduate Medical School and Hospital, Colum-
bia University.

tFrom the Department of Medicine, Division of Cardiology, New York Post-Graduate Medical
School and Hofspltal, Columbia University.

697

AMERICAN' HEART JOURNAL

ms

.Tnd eight hours. Ten patients also had levels taken at ten and twelve hours, and
i,\\ at twenty-four hours.

The dose of 1.0 Gm. of quinidine sulfate was decided upon because of the
po.-sibility of inaccuracy with the colorimetric method at plasma quinidine con-
centration'i much lower than those afforded by this quantit}'. In order to insure
accurate dosage, the contents of each capsule of the drug had been carefully
weighed.

Two ambulatory patients with paroxysmal nodal tachycardia were also
studied over a period of four and one-half months, during which time obser^'at^ons
were made on the relationship between varying plasma concentrations and
therapeutic effect. A therapeutic regime was established for both patients in
which a fi.xed dose of quinidine sulfate was given at four-hour intervals, day and
night, for periods of from three to four weeks, during which periods stabilized
plasma levels were obtained. The dose of the drug was progressively reduced by
25 per cent with each successive period. Blood samples were drawn from
four to twelve times a week, usually three hours after the nearest dose. An
inquiry into any symptoms and a recording of the pulse were made at each
bleeding. Occasionally the effect of exercise upon the pulse rate was also re-
corded. Electrocardiograms were taken whenever an attack of tachycardia
occurred and following reconversion to regular sinus rhj-thm.

RESULTS

/. Plasma Conceutratiovs Attained in Nineteen Patients After a Single Oral
Dose of Quinidine Sulfate. — ^Table I and Figs. 1 and 2 show the relationship of
plasma concentration to time after a single oral dose of 1.0 Gm. of quinidine
.«ulfate. The patients on whom data are given in Fig. 1 had the eight-hour

DELEVETT AND POINDEXTER : PLASMA CONCENTRATIONS WITH QUINIDINE 699

Table I. Summary of Pertinent Data on Each of Twenty Patients Given 1.0 Gii

OF Quinidine Sulfate Orally

i

Patient

1

2

3

4

5

6

7

8

9

10

Sex

M

M

M

F

M

F

F

F

F

F

Height

5' 9}4"

5' 4"

5' 4"

5' 4"

5' 3"

5' 5"

5' 5"

5' 1"

5' 1"

Weight

151

143

137

185

135

112

132

106

101

Quinidine blood levels '

i

(mg-./liter plasma)

15 min.

0.00

0.48

0.12

0.12

0.00

0.28

0.20

0.00

1.28

0.00

30 min.

0.20

2.88

1.44

0.00

0.00

1.68

0.60

0.00

2.68

1.68

45 min.

0.48

2.08

1.96

0.40

0.24

1.50

0.88

0.12

3.66

2.88

1 hr.

0.52

2.28

2.04

0.70

0.68

1.84

1.52

0.28

3.72

2.88

2 hr.

2.04

3.36

2.12

2.76

0.92

2.0G

3.52

1.28i

2.88

3.64

■ 3 hr.

2.08

3.12

2.04

2.84

1.52

1.80

3.48

2.28

2.24

3.84

4 hr.

2.04

2.48

1.80

3.40

1.72

1 80

2.76

2.40

1.92

2.92

6 hr.

2.00

1.92

1.68

3.00

1.08

1.52

2.04

2.04

1.40

2.08

8 hr.

1.90

1.32

1.08

2.12;

0.72

1.12

1.68

1.32

0.92

1.16

10 hr.

0.72

1.04

0.92

0.48

0.84

12 hr.

0.42

0.88

0.72

0.36

0.44

24 hr.

0.16

0.28

0.00

Maximum level

2.08

3.36

2.12

3.40

1.72

2.00

3.52

2.40

3.72

3.84

Time of maximum level

3 hr.

2 hr.

2 hr.

4 hr.

4 hr.

2 hr.

2 hr.

4 hr.

Ihr.

3 hr.

Percentage loss in

plasma concenlra-

lion frotn lime of

1

dose

6 hr.

439^

21%

12%

37%

24%

42%

15%

62%

46%

8 hr.

9%

60%

50%

37%

60%

44%

52%

45%

75%

70%

12 hr.

8^%

75%

70%

87%

90%

24 hr.

92%

92%

.100%

Patient

1

2

3

4

5

6

1

7

8

9

10

Patient

11

12

13

14

15

16

17

18

19

20

Sex

F

M

M

F

M

M

F

M

F

F-

Height

5' 5"

5' 9"

5' 3"

5' 3"

5' 11"

5' 2"^

5' 8"

5' O''

5' 1"

Weight

119

172

146

99

140

111

129

114

92

Qttinidine blood levels

1

(mer./liter plasma)

15 min.

0.36

0.20

WJliJi

0.48

30 min.

0.96

o.nr

0.40

0.96

1.4^^

0.44

0.20

0.72

45 min.

1.56

1.20

0.88

1.32

2.56

1.8'’

i 1.24

i

1 hr.

1.4^

1.56

1.40

1.52

2.56

2.92

1.72

1.12

3.36

3.88

* 2 hr.

2.04

2.56

2.72

2.84

2.08

4.32

1.48

3.88

3.72

3 hr.

2.56

2.88

2.44

2.48

2.40

4.32

1.4''-

2.56

4 hr.

2.44

2.48

2.20

2.12

1.68

3.72

1.36

2.96

3.44

6 hr.

1.68

2.08

1.68

1.72

1.32

2.84

8 hr.

1.2'^

1.4^

1.32

1.28

0.72

i

2.79

0.88

1.72

1.36

in hr.

0.64

1.12

1.2^

0.76

0.6^

12 hr.

0.32

1.16

0.92

0.44

0.12

1.76

24 hr.

■iMiU

n.2'3

0.00

1

Maximum level

wfiag

2.88

2.72

2.84

2.56

4.32

1.48

3.88

3.88

Time of maximum leve’

3 hr.

2 hr.

2 hr.

5^ hr.

3 hr.

2 hr.

2Tir.

1 hr.

Percentage loss ' in

1

plasma concenlra-

lion from time of

dose

6 hr.

34 0^

40%

4e<?t

48%

34%

8 hr.

53^-

51^

51%

5507-

71%

47%.

40%

56%

65%

12 hr;

880^

60%

66%

Sdo/.

95%

75%

i

24 hr.

92%

inr%

96%

Patient

11

12

1

14

15

i 16

17

18

19

I 20

1

1 ^ 3 4 5 6 7 8 9 10 31 112

Tiroe inlio-urs aficr oclwiws-trftlriQji.

l-'lR. 1!.-— TIu* middle cun'o repn'sonts tho avcrnpo concentration at each time period of the sixteen
iirinfastInR patients. The upper curve is that of the patient ivho attained tho highest plasma con-
centratioii among tlie sixteen patients. Tho lower curve is that of the patient wlio attained tho minimum
plasma concentration among the .sixteen patlent.s.

15 10 2

13 14-

5 II 17 12 6 3
Cose 3riuni\) ex

18 19 20

. i.T. Mtotsjiip He- ptir e^'tit lo-’* in maximum plasma concentration at six. eiglit, twelve, and
h-Atr- in paiienjs given a Klnate oral dose of 1.0 Gtn. of qulnldine fulfate.

U»r.. j j.t r relit, lo--. at tiours; horlrontal. per Cent lo«s at elgltt hours; stlpplKl. per cent
' ». tfcj.vt- rroY'. hatch. piT cent Uk.? at twenty-four hours.

DELEVETT AND POINDEXTER : PLASMA CONCENTRATIONS WITH QUINIDINE 701

fast before and after the dose; those on whom data are given in Fig. 2 ate the
usual hospital diet. In both groups there was a considerable variation in the
maximum levels attained, in the times of maximum concentration, and in the
rates of fall. Maximum concentration was reached between two and four hours
in 84 per cent of the cases studied. (Hiatt,® also using the Brodie colorimetric
method, found the maximum concentration was reached from three to four hours
after the oral administration of the drug.) No regular correlation between bod}^
weight and the maximum plasma concentration was observed. As for the marked •

Pig. 4. — A 56-year-old white man, showing the relationsliip between dosage of quinidine sulfate,
quinidine plasma concentrations, and the occurrence of nodal extrasystoles and paroxysmal nodal tachy-
cardia. The diagonally lined blocks in the area of plasma concentration represent the occurrence of
extrasystoles, while the solid blocks indicate the occurrence of paroxysmal nodal tachycardia. In the
area of daily dose, the solid blocks represent single large doses of quinidine sulfate given to raise the
plasma concentration rapidly.

Blank, dose every four hours; diagonal lines, dose every six hours; stippled, dose every eight hours;
horizontal lines, dose every twelve hours.

variation in rates of fall (Fig. 3), by six hours the majority of levels had fallen
between 20 and 40 per cent, with extremes from as low as 4 per cent up to as high
as 62 per. cent. By eight hours the fall was between 40 and 60 per cent, with
extremes from 9 per cent to 75 per cent. Of the eleven patients whose levels
were taken at twelve hours, all had fallen 60 per cent or more. At twent 3 ^-four
hours, seven of these patients had levels which showed a fall of over 90 per cent
in each. There was no apparent correlation between maximum plasma con-
centration and the rate of fall. Complete data for all patients is given in Table I.

U9>ijur^ilrac^us>';)

702

AMERICAN' HEART JOURNAL

2. The Therapeutic Range of Plasma Concentration in Two Patients With
Paroxysmal Nodal Tachycardia.— Two patients with paroxysmal nodal tachy-
cardia were studied to determine the correlation, if any, between the attack-rate
frequency and various plasma quinidine concentrations. Both patients had

I

U

u

<0

2.S’:

\S:

0.S-

i

rL'. Cl — A ll-yi'ar-olrl (vliiio woman. Klionttm ri'lationsliip tioiwiv-Ti <Iall.v doso of (luinldino KUlpliiUe,
conrcntrailon. and tlio oerurmnee of paro.nysin.a) nodal tachycardia. The solid hlock-s
ittiUratf ttiese ntincH-i. The djaconally Un<-<l blocks represent single Inrf-’e doses of qninhline .siilf.ne
iaNf'a raise the blood level rapidly.

tH-en followed for some time before the present study was begun. One of
these, fi. B..* was a man 56 years of age who had had documented paroxysmal
nodal tachycardia for twelve years, with almost constant attacks for the pre-
vious thrct* years whenever he was ambulatory. During the year preceding thi.s
study he had Imhui unable to work. 'lachycardia was even so frequent and
marked that he was obliged to stop several limes during Ins daily shave to sit
dov.ji and r<-s;. There was no evidence of organic heart disease. The other

* t'lasTsiy rrjtircntrKttont

durltii: ih<' Jirflimlnary studies on
1 by !lrtw!ic<

thi<: paticni v.crc dctcrtniitc^l

by the

DELEVETT AND POINDEXTER: PLASMA CONCENTRATIONS WITH QUINIDINE 703

patient, S. F., a woman 41 years years of age, had had attacks at least once
every three weeks, and frequently they had come as often as several times a day
over as long a period as a week or ten days. She also had no evidence of organic
heart disease.

After a suitable control period was established, during which time the
frequency of attacks was documented, quinidine sulfate was started and given
to the patients every four hours at a set dosage sp that a uniform daily total intake
of the drug could be maintained for varying periods* (Figs. 4 and 5). Plasma
quindine concentrations above 1.0 mg. per liter were coincident with absence of
attacks. Dosages which produced plasmale vels below 1.0 mg. per liter resulted
in a recurrence of frequent attacks. Correlation of attack onset and plasma level
was easily reproducible in these patients. (As shown by Figs. 4 and 5, in the
male subject the arrhythmia appeared when the plasma levels ranged between

0.32 and 0.76 mg. per liter, while attacks were present with plasma concentrations'
of between 0.28 and 0.84 mg. per liter in the female patient.) Although this
data dPes not establish an absolute critical level for all such patients, it suggests
that such a level exists. Determination of critical plasma quinidine levels by
means of the methods outlined in this paper is suggested as a basis for rational
approach to the control of paroxysmal tachycardia.

SUMMARY AND CONCLUSIONS

1. By the use of Brodie’s colorimetric method for plasma quinidine concen-
tration determinations, levels were run on a series of patients who had taken a
single large oral dose of quinidine sulfate.

2. There is a marked individual variation in maximum plasma quinidine
concentration following a large single oral dose.

3. The time of maximum plasma concentration varies widely in different
patients, from forty-five minutes to four hours after administration.

4. The rate of fall of plasma quinidine concentration varies markedly from
patient to patient and apparently bears no relationship to the initial maximum
level.

5. The correlation between plasma quindine concentration and therapeutic
effectiveness in two patients with paroxysmal nodal tachycardia is presented.

REFERENCES

1. Weiss, S., and Hatcher, R.: Studies on Quinidine, J. Pharjmacol. & Exper. Therap. .30;

335, 1927.

2. Weisman, S. A.: Further Studies in the Use of Quinidine in the Treatment of Cardiac

Irreprularities, Minnesota Med. 27; 285, 1939.

3. Weisntan, S. A.: Studies on the Time Required for the Elimination of Quinidine From the

Heart and Other Organs, Am. Heart J. 20: 21, 1940.

4: Brodie, B. B., and Udenfriend, S.: The Estimation of Quinine in Human Plasma With a

Note on the Estimation of Quinidine, J. Pharmacol. & Exper. Therap. 78; 154, 1943.

5. Hiatt, E. P.: Plasma Concentration Following the Oral Administration of Single Doses

of the Principal Alkaloids of Cinchona Bark, J. Pharmacol. & Exper. Therap. 81: 160,

1944.

6. Brodie, B. B., and Udenfriend, S.: The Estimation of Basic Organic Compounds and a

. Technique for the Appraisal of Spec'ficitj^ J. Biol. Chem. 158: 705, 1945.

*Th.c occurrence of attacks in G. B. when both daily dose and the interval between successive doses
was frequently varied is indicated in the first portion of Fig. 4. All the plasma levels wore taken from
three to four hours after the preceding dose and nrobably represented the peak concentrations attained
on these schedules. Since there were undoubtedly much lower concentrations at six. eight, and twelve
hours, the attacks may have resulted from these lower levels. Therefore, a four-hour schedule was
initiated to prevent such wide fluctuations in plasma concentrations.

TOE EFFr-:CTS OF THE INGESTION OF LARGE AMOUNTS OF SODIUM
CHLORIDE ON THE ARTERIAL AND VENOUS PRESSURES

OF NORMAL SUBJECTS

Harold Grant, M.D., and Francis Reischsman, M.D.

Dallas, Texas

U NTIL reccnily the most widely accepted explanation of the pathogenesis
of edema in acute glomerulonephritis was that, due to an increase in the
capillary permeability throughout the body, there was an increased amount of
transudation of fluid into the extracellular space. The evidence to substantiate
this view was contained in the work of Beckmann,’ who showed that the edema
fluid in four patients with acute glomerulonephritis contained an increased amount
of protein. These protein determinations were done by means of a refractometer.
Recently. Warren and Stead,'* using a much more accurate method, found no
increase in the protein content of the edema fluid in ten patients with acute glom-
erulonephsitis. Thus, increased capillary permeability could not have been
a factor in the production of edema in these patients and another explanation
will have to be given.

In 194-1 LaDue^ made several verj' interesting observations in twelve
patients with acute glomerulonephritis. He found edema, increased venous
pressure, and cardiac dilatation in all of the twelve and interpreted these changes
as being due to congestive heart failure most likely caused by the arterial hyper-
tension. The question has arisen whether the picture presented by these patients
is due to cardiac failure or is due to the abnormal retention of salt and water by
the damaged kidneys. The question of the relationship of the salt intake to the
level of arterial filood pressure will also be considered.

Grolhnan and co-workers’’ have shown that in certain ca.ses-of h>’pertension
very rigid re.-^trict ion of the sodium intake will cause a fall in blood pressure.
However, (jrollman. Harrison and Williams" demonstrated that an increase in
the intake of sodium by hypertensive rats did not cause any further rise in
arterial pressure.

In this study the efTects of the ingestion of an excess amount of sodium
chloride irr normal adults was observed.

tS O'
fg th

5 hi- liealthy nu-dica! students and physicians ranjjing in age from
■> '5 ‘H'-ev were permiltcd to continue (hdr norma! activities throughout thecourse

r After a control period of two to four days, the administration of 20 to 30 Gm.

■f-.ism c5i!nri-!e per day. taks-n in the form of l.t! Gm. enteric-coated tablets diviiied into four
•:v aisproximately .-quai do-es, v.a.-^ starter!. Noattenipt was made to regulate the salt intake
a- shit and tluido v, e: e allnwr-fi ad lilntum.

th*

!ir

Df‘rt:-.r5r’>>'rit of .Mi-jiSeiiie. .'-’outlnve^tem Medical Oollcjte, and rarKIarid Jlospltal.
a rtafiS frsxn tite Onrfan fntjndatlnn Binl ttie Jnhn and Mary U. Markle Foundation,
f.ir r.*>t.t!eaUon Aprs! 27, loto.

70-1

Table L Changes That Followed the Ingestion of Large Amounts of Sodium Chloride (First Three Subjects)

GRANT AND REICHSMAN ; INGESTION OF SODIUM CHLORIDE

REMARKS

20 Gni. NaCl q. cl.

20 Gni. NaCl q. d.

uuu

o rt o

p p

666

o o o
re ro

fc!

o C

O 3

o ^

, cn

S H
" ci

- 107/70
104/62

107/67 1
106/66 )
110/68 j

^ 1- .. ^

CO VO O -Ti-

VO O t^vOi^OO

O vO OVOl^VOO

^ O CM O O

^

116/72

110/70

108/72

115/70

SERUM

CHLORIDES

(meq,/l.)

<

106.2

112.5

.

URINARY

CHLORIDES

(24 HR.)

6.610

7.250

3.150

5.280

21.920
33.480

20.920

17.350

17.720

FLUID

OUTPUT

(c.c.)

1,190

1,465

1,355

2,310

2,660

2,930

2,530

1,870

2,3.30

INTAKE

(c.c.)

4,000

4,620

4,500

3,550

4.450
4,310

3.450

2,480

3,. 300

VENOUS
PRESSURE
(mm. ILiO)

O lO Ov 1 lO
VO 1 CM

00 vO CO ! ro O O

00 00 00 I r-i CO lo

VO O oo 1 lo C 1 1

-:*< l.~ VO j t." ^ j j

WEIGHT

(kg.)

58.25

58.50

58.75

58.75

58.75

lo o o lo o

CNJ lO lO CM CO lO

00 CO. 00 CO Cv CO Cv
O O .O O O VO VO

.

70.75
71.00

70.50
71.00

72.25

71.50

71.75

71.25

71 ..50

DATE

1 r-. CO

..CM <M CM

x '■

00

,CMCM

lO vD CO O' O
. CM e^j c^j CO ^ o? CO

^ vO vO O VO vO vO

G

705

UCJU

rt r: rt

'Z.'K.'Z.

iiz

oco

O om

ro —

uuu

rt c: rt

'Z'Z.'Z.

660

uuuu

d rt R c:

E c £ c
OOOC

! i

I §“!

i 1 ~i

i 4 'J 1
I !; u
5'-' i

I 1

VC

CO 1

sc

■*Vs,

CO

0

C't

«N

-fO

c 0

0 0

0 0

C'l C

0 ^

«>«

— CN

^-M *>4

voirjO'O tOwO »00
ootocsO

fo^o 1^0

0000 000 00

— VQOOO tO-T •

-rsc«-^ ^ro

^ <M

a

0

to

CM i

51

o o

VO

C\ « ^o
cs cs

I

I

00^
osr^co
•— CO

VOOOC
VC 00

o o 00

1^5 o O

VO O CC CO
cs ic 'O

to 0 to

0000

00 CO

NO — * VO

CM 0

to ^ — CO

CM CM CM

PO «o to

^ ^ i

i

E = * 5

**^ o !

vi ^

< o 5 :i

s o o o
> 00 m rs
» t>. 10

00 00

O ^ to VO

O CV| 10

VC o o 00

^ c-t — *

00c
to ro
ro UO 00

0000

Cv fO 00 O
VO C'J to to

— < r}« r**

c^j CM

£ r? U cJ

iJu !

=^^ 5 i 1

tn^

41.0

0

cc

to

0

0

O'

CO

r *4

C'l

to

S S U

5 q

5 :: u

VO 1 •*■ I

f \C to 1

I Si2 j S

o c* o to

*0 O to
CO CO

*0 O VC ’C

I'* CO c c

. -^ { *^4 t'O

C; vC nC*C

f c 0

0

000

! *='

t

10 to t-o

00 j

! c- 00

j 00

CM fM

•oto i

• VO ‘O'

1 VO

VO VC SO

vOvC 1

^

-fCfCjC

00

C

VO

VC

0

CV-1

CO

0

0

«...

vd

‘

to

0

0

fM

to

10 i

0

c

10

to

r't

<0

0

0 i

c

-O’

CO i CO

VO ttC 0

0 0

to ♦O J'* •

1

000

cocci

— CO

C to fO 1

0 CO 0 *

C C — ■ oi !

r** vC t''

I>« (

1

.coo o
* ?*

• sc ’C vC

0.640 2,185 2,035

3.430 2,760 830

UUU

rt rt cs

p g s
ooo

O lO CM

CM CN

uou

c3 rt ci

'z'z:z

E g !=

ooo

lO lo C^I
CM CM ~

OOO
to to O

O COV

ooo

lo lo lo
CN Cv

lo O lo o

CS O fO

O O C30t^

ooo

COv -rt* CO
VO O CM

O lO o
0\

O CN

OOOO
O oot^t^

\0 to o o

CN ro CS

cs

C^l to to C^J

ro VO 00
r}^ to

cs

asC\ooo

r- 00

ro to
rs

O Ot^ 00

o »C> to to VO to to

OCNi~ Orl<0
•C^ OO VO Cvt^OO 00

to CO VO t~tOT}< ■,-<

O O O CO •“! CM

o

o

lO

d

o

o

o

'O

to

lO

o

o

lO

cs

OO

Cs

CN

o

o

o\

00

•

tn

lOOO

to o o

ooo

CVJ ^ o

CN 00 00

O to

CN O O

O c?v Ov

Cv OvOO

VO

VO VO

VO VO VO

CO to -ij' to VO o

ooo O ■>-' CM —I

00 00 OO OO C» 00 00

COC?vO
■.-I CM

CO rt to voi^ 00
^ C^C^^ C^C^C^

7/30 78.8 4,420 875 112/78

7/31 80.5 4.850 840

7m

A.'.fERICAN HEART JOURNAL

A.!! -tibjtct' ''vrc 'Ari^hed every clay at the same time in the postaclsorptive state. Venous
p;. -ere v.a- <U terniimd by the direct method after a rest period of approximately thirty minute.s.
\t rh<* ':anii t!m<% jiuist- rale and arterial blood pressure were recorded. In five of the subjects
additional <:ttidi< s of the changes in body fluids were made. The daily fluid intake and urine out-
put v.tre mta'-ured. Blood volume determinations were carried out by the dye method, using
The ampoules containing an accurately measured amount of dye, as devised by
Gre;;tr-t'n.‘ v. ere used. A period of ten minutes was allowed for mi.xing, and five samples were
taken at ten-minute intervals in heparin-wet syringes. Simultaneously, changes in the volume
of extracellular fluid were estimated by measuring the "thiocyanate space" according to the
frejlirwi of Crandall and .\nderson,® employing the following formula^:

•‘Available fluid”

CNS injected (mg.) X 100
CNS in blood (mg. %)

Fifty mttuUe-5 were allowed for mixing and all measurements were done in duplicate. The plasma
chloridta were calculated by tlie titration method. Determinations of the hematocrit and of the
total serum proteins were made. In three of these subjects, the twenlj'-four Iiour urinary chloride
output was measured.

The data obtained are pre.sented in Tables I and II. The first two subjects
in Table I (H, G. and F. R.) took sodium chloride for a period of two weeks, but
since no e.ssential change in the weight nor venous prc.ssure was noted after the
bnirth day, the subsequent subjects were given salt for three or four days only.

TAiii-t: III. CiiAN<;t:s Oii'-i.Kvi’D Dcring thp Phriop or High Sodium Intakk

i

t

: 1

VtZNOUS i

1

VUSSMA

r

R. n. c.

> * ** 1

III.OOD

TinOCYANATi;

I’l.AS^tA

‘•t'HJt Ct

1 wi.ir.iir

I I'RUSSURl, j

1 VODUMi;

VOI.UM1.

voi.uMi;

SPACK

CIILORIDK

1 IKU.)

1 (MM. ItjO) 1

I (c.c.)

fc.c.l

(c.c.)

(C.C.)

(MG.)

4-0.25

i -fSO 1

1

1

i

!

1

1

F, R. 1

1 - 1 . 00

■f6I

' i

1

i

1

1

D. B.

1 4-0 75

-^-126 ,

i

1 i

1

1. c., i

s

-rl 15 i

-^58

4 700 1

1

4-200

-4-900

: 4-1580

4-3.5

\V. H. '

-0 00 ,

4-21 i

4-650

"r ISO j

4-S.50

4-2490

4-1 5

N‘. K. :

i -2 20 I

: 62

4-6.10 1

1

1 1

! -f20 !

4-650 !

4-1070

-f-20.1

1. H

i-0 .sS

-- 25 I

■v !

-r 70

-.560

-.520 i

4- .5260

B L

. -t so .

i 1

-61 ■

1

-*-4.10 !

-20

4-410

t

1

4-1550

^4-2.7

In r.ible III are listed the changes which took place during the high sodium
chiorid** intake. In the tu'e subjects on whom more complete circulatory meas-
urrmfuit'. Were made, change.^ were calculated from the data on those days on
vhiilt the blood volumes were determined. In the remaining three subjects,
Che l.ti- <1 ty of she f-ontnil period and the day of the maximal change in venous
prs ' lire v.f Te taken f<jr cotnp.uison.

• Ul of the shfmrd a gain in weight which varied from 0.25 to 2.20

S' ooAf.jnt'.

n-mge- in the venous pres.sure from -f2I to -4-126 mm. of water

GRANT AND REICHSMAN: INGESTION OF SODIUM CHLORIDE 709

were observed.* Changes in the piasma volume were from + 70 to + 700 c.c.;
in the blood volume from —320 to +900 c.c. ; and in the "thiocyanate space,”
from +1,070 to +3,260 cubic centimeters. There were no significant alterations
in the arterial blood pressure. The changes observed are presented in graphic
form in Fig. 1.

Fig. 1. — Effects of ingestion of sodium chloride.

The variation in venous pressure during the period between two doses of
salt was studied. In the first experiment venous pressure curves were done with
the subjects (F. R. and H. G.) in a recumbent position. After the administra-
tion of salt for several days, each subject took 6 Gm. of sodium chloride and 660 c.c.

;*The rise of 126 mm. was observed in subject D. B., an apparently healthy medical student. The
control readihgs ranged from 138 to 170 mm. of irater. His past history was negative with regard to
cardiovascular and renal disease; findings on physical examination were normal, and teleroentgenography
and fluoroscopy of the heart and great vessels revealed no abnormal findings. Urine analysis and Fish-
berg concentration test were normal.

7fO

.UfEJilCAX HEART JOURNAL

r)f water by mouth, and \enous pressure readings were taken at frequent intervals
through a needle which was left in place and kept patent by a 5 per cent glucose
drip at the rate of !5 drops a minute. The same experiment was later repeated
but with the subjects ambulatort* between venous pressure readings done by
multiple venepunctures. The results are presented in Fig. 2. There was a
.‘'iriking difference in the behavior of the venous pressure in the two experiments.

Fit' 2.“Vc'i()ii*! prrssuri' curve's nftfr or.il «lo<;o of sodium chloride durluR hlgli salt intake.

With the subjects recumbent there was a short initial rise followed by a sustained
drop to a level below the initial reading, and both subjects had a diuresis through-
out the experiment of approximately 1,200 c.c. each. If the subject remained
ambulatory between venepunctures, the initial rise in venous pressure was well
''Ustained and diuresis did not occur.

'I Xonc of the eight subjects showed a significant change in arterial blood
pt f'-Hue as a re.sult of the increased intake of sodium chloride.

DLSCU-SSION

A Very similar experiment to that reported here was carried out by Lyons,
J.i* ub^on, and Avery.” In S(,wen subjects, after taking 40 Gm. of sodium chloride
in forty eight iiour.s, the average weight gain was 1.9 kg. and the average rise in
\enotiv prt>..ure, 31 millimeters. These result.s are quite similar to those ob-
in thin experimeni where the average weight gain was 1.04 kg. and the
«. -t .a. e- rs*-!' in wnous pressure, 59 millimeters. The amount of salt was greater
.'.un du> duration of obM-rvation longer in this present study.

f evident that when .'t normal person ingests an e.\cess of sodium chloride
.imbulatnry, the kidneys do not excrete it all, and the isotonicity

GRANT AND REICHSMAN : INGESTION OF SODIUM CHLORIDE ,711

of the body fluids is maintained by a retention of water and a subsequent
increase in the blood volume and volume of extracellular fluid. The change in
plasma protein is much less than the expected fall due to the increase in plasma
volume, as noted also by Lyons, Jacobson and Avery.^^ This is evidently due
to quick mobilization of plasma proteins from storage depots, so that there is
actually an increase in the total circulating protein. This rise helps maintain an
increased blood volume and the higher venous pressure observed.

In patients with acute glomerulonephritis, during the development of edema
there is oliguria and, perhaps, anuria. The question as to which is primary,
the edema or the oliguria, remains to be answered. In the twelve patients
reported on by LaDue,® all had edema, increased venous pressure, and cardiac
dilatation. He interpreted these changes as being due to congestive heart failure
brought on by the acute h3'’per tension. However, all of his patients had normal
or fast arm-to-tongue circulation times, and the dyspnea and orthopnea were
not as prominent symptoms as would be expected if the heart failure were caused
by hypertension. It is quite possible that the changes observed in some patients
with acute glomerulonephritis are related to the changes seen in normal sub-
jects who are fed an excess of sodium. The latter group showed an increased
blood volume, increased extracellular fluid, and a rise in venous pressure.

There have been very few observations on the blood volume in acute glom-
erulonephritis. The most extensive series was reported by Litzner,’® who meas-
ured the blood volume by use of a dye method in six patients with acute glom-
erulonephritis while edema was present and again after diuresis. All of these
patients showed an increased blood volume which then fell to normal levels when
they became free of edema. Calculations of the heart volume were made in
five of these patients and all had cardiac dilatation which disappeared when the
blood volume became normal. Harris and Gibson® reported the blood volume
of four patients with acute glomerulonephritis but did not mention the presence
Or absence of edema. Only one determination was done and the result compared
with expected blood volume as calculated from the patient’s height. Two of
their patients were found to have normal blood volumes. The other two showed
blood volumes which were low, but both of these patients had plasma albumin
levels which were very low.

We have recently observed two cases of acute glomerulonephritis. Both
of these patients had high venous pressures while edema was present; after diuresis
the venous pressure returned to normal levels. However, the fall in blood
volume in both of these patients after the edema had disappeared was rather small :
100 c.c. in one instance and 200 c.c. in the other. Neither patient complained of
dyspnea nor orthopnea.

In acute glomerulonephritis there is an oliguria which at least in some pa-
tients may be due to the pathologic changes in the kidneys. Water and salt
are retained, with a subsequent rise in blood volume, venous pressure, and volum.e
of extracellular fluid. The increase in heart size in these patients may be due
to the increase in blood volume and venous pressure and greater diastolic filling.
That true congestive failure with pulmonary congestion, gallop rhythm, and pro-

712

AMERICrXX heart JOURNAL

longed circulation lime occurs in some cases of acute glomerulonephritis is not
denied. However, in those patients who do not show pulmonary congestion,
gallop rhythm, nor prolonged circulation time, it seems not unlikely that die
abnormal degree of hydration observed in acute glomerulonephritis is, for the
most part , caused by the retention of salt and water by the diseased kidne^-s rather
than by cardiac decompensation. Up to the present time, blood volume studies
have not given con^•incing e\ddence for this hypothesis.

As has already been observed in rats," an increase in the intake of sodium,
at least in the doses indicated, does not cause any significant change in the arterial
blood pressure.

CONCLUSIONS

1. Normal adults show an abnormal state of hydration when fed an excess
of sodium chloride. This slate is characterized by an increase in blood volume,
venous pressure, and volume of extracellular fluid and may closely simulate the
phenomena observed in congestive heart failure.

2. It is suggested that the edema in those patients with acute glomeru-
lonephritis who do not exhibit pulmonary congestion, gallop rhythm, nor pro-
long circulation lime is caused by the retention of salt and water by the diseased
kidtieys. Thi.s also leads to an abnormally high degree of hydration in which
there is increased blood volume, venous pressure, and volume of extracellular
fluid.

3. The addition of 20 to 30 Gm. of sodium chloride daily to the diet of nor-
mal adult.s does not cause any significant change in the arterial blood pressure.

The auliiors wish to ONprt'?s their apprcci.ition to Dr. Tinsley R. H.irrison for iiis help and
guidance in this study.

REFERENCES

1.

2 .

t.

5.

6.

S.

0

m.

It.

u.

Ikrkman, K.: Edema, Deut.'-ches Arch. f. klin. Med. 1.1.'); 39, 1921.

Crandall, L. A., Jr., and .Anderson, M. X.; Estimation of the Stale of Hydration of the
Body bv the .Amount of Water Available for the Solution of Sodium thiocyanate,
•Am. J. Digfist. Dis. & Nutrition 1; 126, 1934.

Gibson, J. G.. Jr., aiul Evelyn, K. A.: Clinical Siudic.« of Blood A’olumc; .Adaptation of
Method to I’hotoelcctric Colorimeter, J. Clin. Investigation 17: 153, 1938.

Greger>en, .M. f.: Practical Method for Determination of Blood t^olume With Dye T 1824;
Survev of Present Basis of Dve-Mcthod and Its Clinical .Applications, J, I^b. & Clin.
Med. '29; 1266, 1944.

Gr(“,^CTsen, M. I., anti Stewart, J. D.: Simultaneous Determinations of the Plasma
t'olume With T 1824 and the "Available Fluid" Volume With Sodium Thiocj’anatc.
Am. J. Physiol. 12.5: 142, 1939.

Gsnlhnan, .A., Harrison, T. R., Mason, M. F., Baxter, J., Crampton, J., and Rcichsman, F.:

Sovlium Rv'iriction in the Diet for Hypertension, J. A. Al. .A. 129; 533, 1945.
Grnliman, Harrison. T. R., and Williams, J. R., Jr.; Therapeutics of Experimental
Hx [lertension. J. Pharmacal. & Exper. Thcrap. 69: 76, 1940.

Harri., .A. W,, and Gibson. J. G., Jr.: Clinical Studies of Blood Volume; Changes in Blood
\oh)n)c in Bright's Disease With and Without Edema, Renal Insufiicienry, or Con-
ks‘'tive Hc.irt Failure, and in Hypertension, J, Clin. Investigation 18; 527, 1939.
UiDue. J. S File Role of Congf-.^tivc Heart Failure in the Production of the Edema of
.Acute Glomt.-ulunephrilis. Ann. Int. Med. 20: 405, 1944.

Lucre r. S.; I-,s.fx*n'men telle tmd klinische Uniert-uchungcn flber das Verhalten der Blut-

rjKnge bei .N'erenerkr.mkimgen. Ztsrhr. f. klin. Med. 112: 93, 1930.

K H . I.'icohsou. S. D., and Averv, X. L.; Increase in tbe Plasma A'olume Follow-
the -Idmini-trafon of Seximm Salts. Am. J. M. .Sc. 208: 148. 1944.

‘ wrs *>■ j . A - und Stmt!, E. .A.. Jr.: The Protein Content of Edema Fluirl in Patients AVitb
.\C!Ue tAomerulonephriti', Am. J. M. .Sc. 208; 618. 1944.

ELECTROCARDIOGRAPHIC PATTERNS IN PENETRATING

WOUNDS OF- THE HEART

Paul H. Noth, M.D.

Detroit, Mich.

INTRODUCTION

TNTERPRETATION of the electrocardiographic patterns following penetrat-
ing wounds of the heart is both interesting and difficult because of the several
factors which may influence the electrocardiogram. The first of these is the
localized myocardial lesion produced by the wound itself. Its electrocardio-
graphic effects might be expected to be unique since there is no exactly comparable
lesion in the various diseases of the heart. Pathologically it resembles myocardial
infarction more than anything else but may be much smaller, usually occurs in
an otherwise normal heart, and often involves the right ventricle which is rarely
affected in myocardial infarction. A second factor which is practically always
present is pericarditis. The mere opening of the pericardium at operation or
the presence of blood or of infection in the pericardial sac may cause pericarditis.
In contrast to the unpredictable effects of the wound, the patterns produced' by
pericarditis are quite characteristic, particularly in the acute stage. However,
even recently these effects have been attributed mistakenly to the wound itself,
and the role of pericarditis has not been recognized. A third factor which is
present in some cases is an area of myocardial infarction due to laceration or
ligation of a sizeable coronary artery, nearly always the descending branch of the
left coronary artery. The combined electrocardiographic effects of the second
and third factors are paralleled in previously reported instances of clinical myo-
cardial infarction complicated by pericarditis^ and experimental myocardial
infarction .2

In addition, several other attendant conditions may influence the electro-
cardiogram. These are shock, anemia, changes in the position of the heart due
to air or fluid in the pleural spaces, and, rarely, the coincidental presence of
chronic cardiac disease. With the exception of the last condition, these effects
are nearly always transient and of insufficient extent to cause confusion in the
interpretation of serial tracings.

The. possibility of recognizing the changes due to individual factors in these
combined patterns has an important bearing upon certain questions about which
there has been a diversity of opinion. The fundamental and most difficult of
these is whether the wound produces characteristic changes and so ma}^ be recog-
nized and located from the electrocardiogram. The question of whether injur>'

From the Department of Medicine of Waj-ne University College of Medicine and Detroit Receiving
Hospital. . Parts of tlie material in this study have been published in the Proceedings of the American
Federation for Clinical Research 1 : 49, 1944, and in the Proceedings of the Central Society for Clinical
Research 17 : 52, 1944, and 18 : 34, 1945.

Received for publication May 13, 1946.

713

71

AMERICAN* HEART JOURNAL

in major branches of the coronary arteries with resultant myocardial infarction
becomes apparent in the elecirc cardiogram is a part of the consideration of localiz-
ing fmdings in such cases. The second question is how often and at what stages
the effects of pericarditis appear. Upon the answers to these questions depend
certain practical decisions such, as the diagnostic value of the electrocardiogram
during the preoperative or early period and its subsequent usefulness as a guide
to therapy and prognosis. Furthermore, these electrocardiographic effects are
of considerable theoretic interest, particularly those following wounds of the right
ventricle.

The purpose of this report is to offer a brief analytic review of the literature,
some of which is not generally available, to present the electrocardiographic
findings in a group of twenty-three patients, and to correlate these with the
results of clinical observations in eight patients re-examined after an a^•erage
period of nineteen months following the cardiac wound.

REVIEW AND ANALYSIS OF THE LITERATURE

General .Scope AND Content. — The electrocardiographic changes following
wound.s of the heart are described in slightly over one hundred cases in the
literature available to me. Fifty articles contain reports of single cases."'"*
Thirty cases are included in the article by Herve and Forero Sarabia.*’^ McGuire
and McGratlff* describe the findings in eleven cases, in one of which the electro-
cardiograms arc published. The remaining cases appear in groups of from two
to four.^’-"^‘ There are five arlicle.s‘^’*'’'’‘^''’®'®^ containing re^'iews of cases, of which
that of Snlovay and co-workers,^’ listing the electrocardiographic findings in
sc\'enteen cases, is the most extensive.

From the standpoint of analysis of the findings, the seventy cases^'”-’'^^’’’®
in which the electrocardiograms are satisfactorily reproduced are the most valu-
able ones. However, the studies in many of these cases are incomplete in one
or more respects. In rwenty-lwo only one electrocardiogram is recorded. In
thirteen the early changes do not appear since the first electrocardiogram was
not taken until after the first week. Precordial leads were taken in only twenty-
two. and in all of ihc.'^e only a single precordial lead was employed. The most
outstanding lack is the paucity of long-term studies. Whereas thirty-one cases
were followed ffir three months or longer, only thirteen were followed for more
than six months.

The Rule of Pericarditis.' — The first definitive studies of the electrocardio-
graphic changes in pericarditis of various ctiologic types appeared in 1929.'’’''
in 1934 the pathogene.sis and evolution of the complete series of changes during
both acme and subacute st.ages were greatly amplified.'’'' It is now well known
iliat pericardiiis in both the acute and subacute stages produces electrccardio-
graphit: changes which may closely resemble those of myocardial infarction.
The tir-i rejvirs in the Fnglish literature of electrocardiograms following wounds
'4’ the heart appeared in 1924,'" before the studies just mentioned and during a
tvteni <,t intense interest in the pattern.s following myocardial infarction. It is
appin at. thcreh.re, why thc-se tracings following cardiac wounds were thought

to b(,'

tfaiTtioa'-- of the myrjcardial lesion and why the ntle of pericarditis was not

NOTH ; EGG PATTERNS IN PENETRATING WOUNDS OF HEART

715

appreciated. However, a definite lag is indicated by the fact that since 1930
at least fifteen reports«’i3-i9.2i.23.25.28, 33 . 3 . 1 . 40 . 41 . 43 . 51 . 63.64 have appeared in which
interpretations of the electrocardiographic findings were made, but in -which the
effects of pericarditis are not mentioned. Eight of these have been published
since 1938. This oversight has caused a great deal of confusion.

- The first mention of pericarditis as a factor in the electrocardiogram follow-
ing cardiac wounds occurred in the report by Elkin and Phillips^“ in 1931. The
following year Porter and Bigger” felt that they had excluded pericarditis as a
factor in their two patients because a pericardial effusion was absent in one and
did not parallel the electrocardiographic changes in the other. They based
thi6 opinion on the then-prevailing concept that pericarditis produced its electro-
cardiographic effects only because of generalized myocardial ischemia created
by the pressure of the effusion on the heart and coronary vessels. In 1933
Eakin” and in 1934 Davenport and Markle^” reported cases in which the tracings
were explained in this manner. Schwab and Herrmann^” included a case of a
bullet wound of the left ventricle in their studies on the electrocardiogram in
pericarditis and first pointed out that the inversion of “coronary” contour of
the T waves during the subacute phase of pericarditis was related to the in-
flammatory process in the subepicardial myocardium. In 1937 Vanderveer
and Norris®^ stated, “The progressive changes in many cases of stab wounds of
the ventricle suggest pericarditis rather than a single anterior lesion of the
myocardium.” The main thesis in this general article on pericarditis was that
their pathologic studies showed that RS-T segment elevations as well as T-wave
changes depended upon subepicardial myocarditis and that intrapericardial
fluid caused inconstant electrocardiographic changes. Wood” expressed the
tentative idea that pericarditis or right ventricular injury accounted for the
changes following wounds of the right ventricle, while those following left ventric-
ular Wounds were due to the localized myocardial damage. In 1938 the present
author®® (and later with Barnes®®), from a review of the published electrocardio-
grams in cardiac wounds, pointed out the superimposition of changes due to
pericarditis upon those due to the wound and, in some cases, also upon the
patterns of myocardial infarction from injury of a coronary artery. WinteVnitz
and LangendorP® stated that the electrocardiographic changes following cardiac
wounds were most often and most noticeably due to the pericardial reaction
and that the direct cardiac injury seldom influenced the electrocardiogram.
In 1940 Forero Sarabia^® and Parade and Rating®® emphasized the prominent
part payed by pericarditis and its effect in obscuring the changes due to the
wound. Solovay and co-workers®^ in 1941 recognized the preponderant influence
of pericarditis during the first two weeks, but after this period ascribed the
inversions of the T waves to the myocardial injury.

- In 1943 Herve and Forero Sarabia®® drew practically the same conclusions.
Their description of the incidence and the types of early changes due to peri-
carditis agrees so well with other cases in the literature that it serves adequately
as a summary of these effects of pericarditis. They found that electrocardio-
graphic evidences of pericarditis were present in twenty-seven of their thirty

716

AMERICAN HEART JOURNAL

patients. The ele\-ated, concave RS-T segments occurred at variable periods.
They v.'ere present during the first six hours postopera tively in four of nine
patients. During the si.x- to twenty-four hour period they were found in nine
of ten patients. After the eighth day the frequency of elevation of the RS-T
segments lessened progressively, and they became isoelectric and convex in
contour. The T waves, previously upright and often e.xaggerated in the leads
in which elevation of the RS-T segments had occurred, became flattened and
then inverted, beginning at the end of the first week and continuing during the
second week. At the end of this period 85 per cent of their records showed
negative T waves in some or in all of the leads in which they were previously
positi\'e. The inversion of the T waves occasionally appeared first in the pre-
cordial lead but usually occurred more or less simultaneously in all leads.

Other authors especially in recent years, have men-

tioned the role of pericarditis.

Localizing Findings. —

General Rcreiciv of the Literature . — In 1935 Koucky and Milles’® stated:
"From the standpoint of the electrocardiographic changes resulting from wounds
on the anterior surface of the heart, the picture varies but little from case to ■
case, regardless of the presence or absence of involvement of the large coronary'
ve«=e!s or of the region of the anterior surface of the ventricle damaged.” In
1937 Wood®-' asserted that if the wound was situated in the anterior part of the
left ventricle toward the apex, or if the anterior descending branch of the left
coronary artery had been ligated, the electrccardiogram usually showed the
"classical Ti pattern” and therefore was almost certainly directly due to the
myocardial injury; if, however, it was situated in the anterior right ventricle,
the electrocardiogram conformed to "the T» pattern,” with early elevation of
the RS-T segment, e.spccially in Lead II, with later inversion of the T waves in
all three leads. He tentatively explained these latter changes either on the
basis, of the hemopericardium or possibly as the direct effects of anterior right
ventricular injuries.

In 1938 Winternit?: and Langendorf^® noted that the cardiac wound itself
>eklom influences the electrocardiogram, although changes due to myocardial
infarction are apparent in .some patients in Avhom the coronary arteries are in-
volved. However, since in their opinion normal coronary arteries withstand
ligation better than sclerotic ones, they felt that the electrccardiogram shows only
whether «ir iku a cardiac or pericardial lesion is jiresent without indicating with
Certainty its site or whether or not a coronary vessel is involved. In the same
year the present atithori^ (and later with Barnes'^'’) found that when the reported
cans, are divided into two groups, those patients with and those without injury
to major coronary v'es.sel.s, certain differences become apparent. Since these
;>r<- included in the present analysis, this point will be amplified later.

In loif) {-orero Sarahia'” declared that the electrocardiographic effects of
{M-fif arditiv "rnaVee imp<jsstblc or hamper a localizing electrocardiographic
Such a diagnosis is possible only occasionally when the electro-

no^r.'rn h.i^. been obtainetl immediately after the surgical intervention or

NOTH : ECG PATTERNS IN PENETRATING WOUNDS OF HEART 717.

long enough afterward so that the signs of pericarditis have disappeared.”
In 1941 several authors commented on the presence or absence of localizing
findings. Bean'* reported a case of a bullet wound of the heart with ligation
of the anterior descending branch of the left coronary artery and recognized
changes which he felt were due to the combined effects of pericarditis, operative
trauma, and the bullet wound. Q-wave patterns suggesting damage to both
anterior and posterior surfaces of the left ventricle were present. Solovay
and co-workers,®* from a review of the electrocardiograms in seventeen cases,
including one case of their own, agreed with Wood’s idea as to the existence
of a “Ti pattern” in left ventricular wounds and a ‘‘T2 pattern” in right ventricular .
■ wounds. They felt that inversions of the T waves after two weeks were due to
the myocardial injur}'- and therefore could be used in its localization. McGuire
and McGrath®* stated in a brief report that in their eleven patients, ‘‘the electro-
cardiographic changes were similar whether the right or left ventricle was injured
and had no localizing value . . . The electrocardiograms in tsvo patients in
whom the anterior coronary artery and vein were ligated were similar during the
first week after operation to the records of the other patients.” The electro-
cardiograms of only one patient in their series are published and the other tracings
are not described in detail.

The impossibility of evaluating localizing changes when the pattern of peri-
carditis is not appreciated is illustrated by Caviness and Turner’s® report in
1943 of a wound of the left auricle, in which they stated that ‘‘electrocardio-
graphic changes incident to injury of the auricles are not essentially different from
those caused by injury to other portions of the myocardium such as occur after
coronary occlusion.” Their series of electrocardiograms showed no changes in
the P waves and no Q-wave patterns, whereas the T waves were inverted and
‘‘coronary” in contour in the three standard leads — a finding characteristic of
pericarditis. ZerbinP® reported on a patient with a right ventricular wound
in whom' the descending branches of the left coronary artery and vein were ligated
about,4 cm. above the apex. He stated that the curves did not reflect myocardial
infarction since there was no Q wave in the precordial lead. In the published
precordial electrocardiograms the R and S waves are of equal amplitude, probably
indicating that the electrode was placed over the anteroseptal portion of the left
ventricle. This case is of interest since it may be comparable with instances of
anterior myocardial infarction in which multiple precordial leads show Q waves
in one or a few leads but not in others. Herve and Forero Sarabia®® modified the
previously quoted statement of the latter of these two authors by pointing out
that the study of localizing patterns permits a genera! idea of common distinc-
tive characters among different groups, left ventricular wounds generally causing
alterations in T waves in Leads I and IV which are more marked and more per-
sistent than the changes in the T waves in Leads II and III. In right ventricular
wounds they sometimes found abnormalities of Ti and T4 but noted that these
changes tended to regress during the second month, whereas the changes in
T2 and Tg persisted for a longer time. Three of fourteen right ventricular
wounds showed either complete or incomplete right bundle branch block. P-wave

71S

AMERICAN HEART JOURNAL

changes of questionable extent occurred in two of the fi\'e auricular wounds. In
ail, eleven of twenty-seven patients presented signs definitely suggesting the loca-
tion of the wtnind. In many of the remaining patients only one or a few electro-
cardiograms were taken. Among eleven patients there was frequently a dis-
crepancy between the location described at operation and that found at autopsy.
The most common error was to mistake right ventricular for left ventricular
wounds. This observation is important because it may explain discrepancies in
sf)me cases between localizing electrocardiographic patterns and the supposed
location of the wound.

Analysis of Localizing Findings in Electrocardiograms Depicted in the Litera-
ture. — There are several inherent difficulties in an analysis of localizing findings
in electrocardiogj'ams depicted in the literature. The first of these is that the
true incidence of localizing patterns can be only roughly estimated because the
electrocardiographic studies are often incomplete in one or more respects. The
second is, as pointed out by Herve and Forero Sarabia,^ that the surgeon’s
description of the location of the wound cannot be relied upon completely.
The third is, during a considerable period of time, that the effects of pericarditis
may obscure localizing findings. To avoid this last difficulty, it has been sug-
gested that tracings taken either ver>' early or considerably later wdien these
efTccis have disappeared should be the most valuable. This suggestion has been
adopted in the present anah’sis though with certain reser^’^at^ons which will be
mentioned.

Casc.s With Early Electrocardiograms: Table I shows an interpretation of
the findings in thirty-one cases depicted in the literature with tracings taken dur-
ing the first twenty-four hours. The word localizing has been used thus far to
indicate changes pointing to the particular part of the heart involved by the
wound. In this sense there are only two patterns which have localizing value
at this smge. The first of these is that of myocardial infarction. When this is
present, it indicates that the wound is in one or the other ventricle but near
enough to the coronarj' artery, nearly alwaj's the anterior descending branch
of the left, so that this artery is involved in the wound or during its suture.
Among the se\'cn patients in the first group in Table I, this was proved to be
present in six anrl con.sidered very probable in the seventh. In three of these,
.1 definite pattern of anterior infarction consisting of a reciprocal depre.ssion of the
RS-'P segment in Lead III, measuring 2 mm., is present. In three of the other
four p.'itients, .similar though le.ss deep reciprocal depressions occurred, but because
of the fart that in a few instances acute pericarditis may show slight RS-T
diepre,-.;\nns in Lead III, these three cases are classified as suggestive rather than
Oiagno'-tic of anterior infarction. One other case is classified as suggestive
ni infarrtion iH cause of the presence of a Q wave in Lead I. In only one of these

patienti. was a precordial lead obtained during the first twenty-four hours,
and in thj^; patient^ the W'olfcrth lead showed a small Q wave which would be
equiva.ent iri .a htnall R wave in the precordial leads now in use. The ab.sence
o. Ate pattern cT infarction in three preoperaiive tracings is due to the fact that
a! o xxirtfA .!■.= .a result of ligation of a coronary artery during the operation.

Infarct.. Infarction; bundle branch block; Perlcard., pericarditis; Myo. Dam., myocardial damage.

Numbers within parentheses refer to the numerical order of the articles in tho list of references. The reference numbers printed in heavy typo indicate
that tho electrocardiographic finding de.scribod appeared in a prooporativo tracing shown in tho article. Dotted linos connect multiple trficings within first
twenty-four hours. In throo other cases two possible intorprotations are listed for each. Tho total 6f interpretations thus exceeds tho nunlbor of cases.

l/\

720

AMERICAN HEART JOURNAL

T'.ra.r, 11. EuxTROCARDiOGUAraic Findings Among the Twenta’-Three Cases Without
Ligation of a Coronara' Artera- Followed Three Months or
Longer Depicted in the Literature

i

1 1

TIME OF

NUMBER

i NUMBER 1

TA PE OF FINDING

FOLLOAV-UP

OF

1 OF LEADS i

i i

(months)

PATIENTS

A . Left Ventricular Wounds {Seven Cases)

.L3L 1

3, 3, 3

Normal electrocardiogram

f 4,4,6

3

.a.'' (Case 2) (
53 (Cast; 17)

3

InA'crted Ti and Ti; Qt

1

1 10

I

IS

3

Inverted Ti ; Qi

1 10

1

3 i

3

Dipliasic Ti

1

—

21 i

3

Low Ti; notched QRS

614

1

|Low Ti: inverted T 4

]

53 (Case 22) |

1

\

1

(Rounded T^; elevated S-'D: small R 4 ;

1

1

!

( low voltage

7 J

B. Rinht Ventricular Wounds (Tu'clve Cases)

IL 19, 20. .33
53 (Case 12 ),
54 (Ca'=e 1)

1 3, 3, 3 1

1 i

Normal electrocardiogram

3, 4, 4,

5, 5, 17

6

K

3 !

Right bundle branch block

3

1

53 (Ca.se 14)

4 i

Right bundle branch block; low Ti;
inverted Tj, 3, 4: R 4 >S 4

4

1

2S

3

Di()hasic Ti: inverted T« and T 3

1

54 (Case 1)

4

Inverted T. and Tj; R,>S 4

3

—

S3 (Ca.«e 0)

3

Isoelectric T*; inverted T 3

3

1

57 (Case 2 )

3

Isoelectric Ti

4

1

31 j

4

Inverted T 4 ; ? Tj; inverted Tj; S 4 > IL

5

1

C. Auricular Wounds {Three Cases)

1

(> i 4 Normal electrocardiogram

n : 3 ‘Isoelectric Ti, j. 3 ; low voltage

5.3 {Ca.«:e 26) | 4 Isoelectric Ti, -, 3 ; T 4 low up

1

3

6

3

1

1

1

D. Rif^lit and Left Ventricle {One Case)

1

23 * 3 Normal electrocardiogram

1 1 :

1

j 6

I

E. 7'otal Cases {Twenty-Three)

1 I

t 1 Normal electrocardiogram j 5.5 (Av.)

; 1 Abnormal electrocardiogram ! 5.6 (Aal)

11

12

1

n’lUdiiiiih' of tlif fli'ilcctlon prctR'dlng t!it‘ Bisn that of th(' th'flcctlon

• MSP*! Ktudh-d at tnon* than otio time after the t hree-nionth porlod.

I rt-rlranUl!'*

noth: ecg' patterns in penetrating wounds of heart 721

The second localizing finding in these early tracings is that of bundle branch
block. This was always a right bundle branch block and- in all instances, except
one in which wounds were present in both ventricles, the right ventricle was the
site of the wound. Since, in several other patients reported on in the literature
and in two patients in the present series, the right ventricle was always involved
by the wound when .this pattern was present, it is considered to be of localizing
. significance.

Other than these two types of localizing patterns, there are no findings at
this time which indicate the part of the heart involved. The degree or location
of elevations of the RS-T segments or abnormalities of the T waves are not dis-
tinctive of a particular location. It is apparent that since definite electrocardio-
graphic evidences of pericarditis are present in eleven patients, pericarditis is
capable of obscuring localizing patterns even at this earl}'- stage. However, if
the word localizing is used in the broader sense of evidence of involvement of
any part of the heart, then pericarditis maybe considered as a localizing finding.
Including it, there are only ten of the thirty-one patients in whom there is
neither definite nor suggestive evidence of cardiac or pericardial involvement.
Of these ten, six showed nonspecific changes which might be expected to result
from shock or anemia, and in four the tracings were within normal limits.

Cases With Late Electrocardiograms : For reasons to be commented upon later
it seems desirable to consider only those in which tracings were obtained three
months or later following the wound. Table II shows the patterns observed in-
the twenty-three patients without known coronary involvement. There are
five wounds of the left ventricle associated with electrocardiographic abnormalities

Table III. Electrocardiographic Findings Among the Eight Cases With Ligation of
THE Left Coronary Artery or Its Branches Followed Three Months
.OR Longer and Depicted in the Literature

TIME OF

NUMBER

REFERENCE

NUMBER

TYPE OF FINDING

FOLLOW-UP

OF

OF LEADS

(months)

PATIENTS

A. Left Ventricular Wounds {Three Cases)

57 (Case 1)

3

Normal electrocardiogram

3

1

12 , ^

4

Low Ti; diphasic T 4 : small Qr, R 4 = S 4

7

1

9 -

4

Low Ti; inverted T 4 ; Q 4 ; S 4 > R 4

6

1

B. Right Ventricular Wounds {Five Cases)

8, 55 (Case 1) i

3

Normal electrocardiogram

3, 8

2

35 - 1

4

Inverted T 4 (R 4 = S 4 )

8

1

4' i

4

Isoelectric Ts; inverted T 4 ; Q 4

RV x-systoles

13

1

22 .

. 3

Diphasic Ti; Qi and Q 2

48

1

x~systoles, extra or premature systoles.

722

AMERICAN' HEART JOURNAL

persisting for three months or longer. In one of these the electrocardiogram
IfC-came normal subsequenth’. All show involvement of the T wave in Lead I,
and only one showed involvement of T*. On the other hand, four of the five
right ventricular wounds with persisting abnormalities other than right bundle
Branch Block show altered T waves in Leads II and III, whereas only two show
altered T waves in Lead 1. The location of the single precordial electrodes in
these patients is presumably at the cardiac apex or in the midclavicular line.
As judged by the relative amplitudes of the R and S waves, the electrode was most
frequently near a point over the interventricular septum where both right and
left ventricular events might influence the direction of the T waves.

Table III shows the electrocardiographic findings in eight cases with ligation
of the left coronary artery or its branches followed three months or longer and
depicted in the literature. The electrocardiogram became normal in three
patients, in all of whom there was no precordial lead, whereas it remained abnor-
mal in five patients, in four of whom a precordial lead was taken. Q waves
were present in the prccordial lead in two patients. In another, a Q pattern
occurred in the standard leads. The patterns in left and right ventricular wounds
are seen to be more alike, as would be expected if the infarcted area was exerting
a preponderant influence.

I’RE.SENT STUDY

Material AND Method. — Electrocardiograms were obtained from twenty-
tltree patients suffering from penetrating cardiac wounds. The number of trac-
ings for each patient varied from one to twenty for each patient but was less
thati three in only three patients; the average number was seven. In two onl}'
the standard limb leads were taken; in five a single precordial lead (IV F) also
was obtained on one or more occasions; in four the precordial Leads V 2 , Vj,
and Ve were obtained in addition to the standard limb leads; in one there were
three .standard and six precordial leads (A'l-Ve); in eleven a total of twelve leads
(three standard, Yi-Vc, and augmented unipolar leads from the extremities)
were taken on one or more occasions. Of the twenty-one patients with one or
more precordial leads, these were first recorded during the first week following the
wound in six, during the second week in five, during the third week in four, and
after this in the remaining six.

The fir.st electrocardiogram was taken preoperatively in two patients,
during the first day in .six, during the second day in five, during the third day
in six, during the fourth day in one, during the fifth day in two, and on the
thirteenth day in one.

In nineteen patients the period of electrocardiographic study varied between
esglucen da^s and three \'ears. In five, this period was one month or less; in
two. it terminated during the second month ; in twelve it extended for three months
or longer. Five patients in this last group had electrocardiograms over a period
e.f fr.>m two to three vears.

Light p.atleius were completely re-examined by me at periods varying be-
tv-v-trs live and thirty-six months, averaging nineteen and one-half months,
f*'yl'>winir tlu' wound Ten paiienUs had follow-up roentgenologic studies.

noth; egg patterns in penetrating wounds of heart 723

The location of the wound was determined at operation in eighteen patients.
In five it was in the right ventricle; in eleven, in the left ventricle; in one, in the
left auricle; and in one it involved only the pericardium and a branch of the right
pulmonary vein. In the five patients in whom operation was not performed,
cardiac involvement was indicated in three by the presence of physical signs
of cardiac tamponade, the fluoroscopic findings of an enlarged nonpulsating
cardiac shadow, and the aspiration of blood from the pericardial sac. In the
other two patients (Cases 19 and 20) these signs were not described, and the
diagnosis of cardiac involvement was based chiefly on the electrocardiogram.

These cases are included in a study on the surgical aspects of penetrating
cardiac wounds by Blau."-

Findings. —

General Findings . — Table IV shows the evolution of the principal electro-
cardiographic changes and their interpretation in terms of the presence or
absence of pericarditis, nonspecific myocardial damage, and localized myocardial
daihage resulting from the wound. The electrocardiograms returned to normal
in six patients. The time of the normal tracing varied between ninety-five days
and thirty- three months, averaging fifteen and one-half months. However, the,
time of the last preceding abnormal tracing averaged only forty-two days, in-
dicating that there was usually a long period between these abnormal and the
subsequent normal tracings. Therefore, these cases do not provide information
as to the length of time actually required for the return to normal. Follow-up
on the six patients with persistently abnormal electrocardiograms (Table V)
was continued for an average period of twenty-one months, which is longer than
the follow-up on the group of patients with a return to normal, so that it can be
stated that the length of the follow-up period does not account for the differences
between these two groups.

Definite evidences of pericarditis are present in seventeen patients. In
seven of these (Cases 7, 9, 11, 16, 17, 22, and 23) no other abnormalities can be
detected. Five others (Cases 5, 6, 14, 15, and 19) showed changes suggestive
of pericarditis. The only one (Case 20) in whom no electrocardiographic evi-
dence of pericarditis appeared is the patient in \vhom the first electrocardiogram
was not taken until the thirteenth day, and the presence of anterior left ventric- ,
ular damage makes it impossible to interpret the inversions of the T waves on
any other basis, even though pericarditis may be a factor.

Patterns attributable to the wound and therefore of localizing value are defi-
nitely present in ten patients (Cases 1, 5, 6, 8, 10, 13, 14, 15, 19, and 20), question-
ably present in five (Cases 3, 4, 12, 18, 21), and absent in the remaining eight
cases. There are ten patients (Cases 1, 2, 4, 6, 8, 9, 13, 14, 20 and 21) in whom,
in addition to patterns of pericarditis and/or localized myocardial damage from
the wound, various changes appeared which are classified as evidences of non-
specific myocardial damage. They include depression of the R-T segment in
one or more leads (three cases), inversion of T waves during the first week in
leads other than those reflecting- the localized myocardial damage (three cases),

TAfinn IV, Evolution of pRiNctrAi- Ei.r:cTROCARDio<;ifApnK: FiiAiORUS

Early ECG’s strongly .
suggestive of peri-
carditis; later, L.V.
myocardial damage
from wound, possibly -
infarction prolonged ^
Q-T, a nonspecific
change

ECG’s show only
pericarditis which
recurred clinically , ‘
at 30 days

Early, pericarditis;
later (18 days and sub-
sequent), L.V. myo-.,
cardial damage; non-
specific myocardial
damage , '

Early stage of peri-
carditis; died seventh- .
day, autopsy: -purulent
pericarditis, non-
specific damage indi-
cated by auricular
fibrillation

Early, pericarditis;
loft ventricular
damage at twenty- .
eighth month

dop., depressed; diph.,
V.D., left axis deviation;
poratlve; Qavp, Q wave
R-T or RS-T segment;

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730

AMERICAN HEART JOURNAL

Tarli: \\ Late Electrocardiographic Fixdings Among Twelve
Patients With Cardiac \^'ouNDs

i I

1

[

TIME OF

NUMBER

CASr 1 NUMBER 1

! OF LEADS j

1 TYPE or FINDING

FOLLOW-UP
(months) I

i

OF

PATIENTS

A. Left Ventricular Wonncls {Six Cases)

13, 12 (Fig. 2)

12. 9

Normal electrocardiogram

<■ 11.30 ‘

2

S (Fig. 6)

12

Inverted Ti, T;, Tvs-d P-R = 0.24 sec.

1 8

1

14 (Fig. 6) i

12

Diphasic Ti.i.vs.e; Tv* low up

1 21

1

10 (Fig. 6) ;

12

Diphasic Tj -f Tv*; inverted Tj + Tve

28

1

*6 (Fig. 5)

12

Inverted Tvs -p Tv®; diphasic Tj-pTv*:
isoelectric Tj; low voltage; dimin-
ished Rvi

36

1

13 i

i

)

12

Low voltage of Ti, Tj, -p Tvo

—

B. Right Ventricular Wounds {Three Cases)

I

3, 4 (Fig. 4) ■

1 (Fig. 3) ^

1

t

i

t

1

6. 12

12

1

1

1

Normal electrocardiogram

Defective intraventricular conduction (in-
complete right bundle branch block),
right ventricular premature systoles;
diphasic Tvs, Tvst inverted Tv* i
(Sv* > Rv*), left ventricular prepond-
erance

1

3. 33

35

1

2

1

c.

Pulmonary Vein and Pericardium {One Case)

1“ (Fig 1) i

!

1

4 ;

Elevated S-T;, 3,3 (recurrent pericarditis)

3

1

1

P. Unhttenen Location {Tuo Cases)

21 (Fig. i),23j

\

12. 12 !

i

)

1 Normal electrocardiogram

1 1

5. 11

1

2

F.. Total Cases (Turhe)

-

j

1

J Normal electrocardiogram

^ 15.5 (Av.)

6

I

i

1 Abnormal electrocardiogram

1 21.9 (Av.)

6

S,* > •” T.ave In V< exceeds R wave In V< In amplitude.

•Probable compllcatlnR anterior Infarction.

atiricular fihrillaiion (two cases), prolonged Q-T interval (one case), defective
intraventricular conduction (one case), and prolonged aunculoventricular con-
duction (one case).

Pcncardilts.—Tha evolution of the electrocardiographic effects of pericarditis
i^- best considered in chronologic order since it follows a fairly regular course and
■'ince it is important to Imow what to expect at a particular stage.

NOTH :

ECG PATTERNS IN PENETRATING

WOUNDS OF HEART ’

731

RS-T Segment Patterns: Of the two tracings taken preoperatively (Cases 11,
15— Fig. 5), the first is within normal limits and the second shows the pattern
of acute anterior myocardial infarction in which it is impossible to distinguish
with certainty changes which may be due to the associated hemopericardium.
There are eight patients with electrocardiograms taken preoperatively and/br
during the first twenty-four hours. In the first patient, j ust mentioned (Case 11),
with an essentially normal preoperative tracing, an electrocardiogram taken eight
hours after the operation shows the characteristic changes of pericarditis. The
findings in the second (Case 15) have been described. In a third patient (Case
17 — Fig. 1), a tracing taken immediately postoperatively showed nonspecific
abnormalities but twenty-two hours later is suggestive of acute pericarditis.
Of the remaining five patients, two show definite pericarditis (Cases 9, 18—
Fig. 1), one suggestive changes (Case 6), and two only nonspecific abnormalities
(Cases 21, 22). Thus, in five of these eight patients, the electrocardiogram
taken during the first day shows pericarditis as early as eight hours postoper-
atively.

By the second day and thereafter during the first two or three weeks, the
characteristic upwardly concave elevations of the RS-T segments were almost
uniformly present. Of the standard leads they involved Leads I and II most
frequently and were present in Lead III also in only one patient. In three
patients this segment was slightly depressed in Lead III. In the fourteen patients
in whom there are sufficient tracings at this stage for analysis of changes of the
RS-T segment, elevations disappear in from eight to eighteen days, averaging,
thirteen days (Figs. 1 and 2). Such elevation appears first in one or more of the
precordial leads in three of the five cases suitable for determining this point.
Ten patients have electrocardiograms with one or more precordial leads taken
at, the same time or within a few days of the time when this segment became
isoelectric in the standard leads. In seven, the RS-T elevation in the precordial
leads disappears simultaneously, while in the other three it persists for a longer'
time in the precordial leads. It is more striking in the precordial leads in eight
of eleven cases suitable for comparison. In general, however, since the RS-T
changes are easily visible in the standard leads in the great majority of cases, the
precordial leads are only occasionally of additional help as far as this feature
is concerned. In two patients RS-T elevation recurred. In one, this accom-
panied definite clinical signs of pericarditis. In the other, no pericardial findings
were elicited, but the patient suffered from thoracic empyema which necessitated
surgical drainage (Case 17 — Fig. 1).

T-Wave Patterns: Abnormalities of the T waves during the days and weeks
following a penetrating cardiac wound may be due to pericarditis, to the wound
itself, or to nonspecific types of myocardial damage from shock, anemia, or other-
less frequent causes. The presence of these multiple factors might appear to
make it impossible to ascribe a particular T-wave abnormality specifically to.
pericarditis. Nevertheless, from a consideration of the behavior of the T waves
in uncomplicated pericarditis of other types, it is possible to distinguish certain
trends of influence upon the T waves of the pericardial factor in the present
series of patients. In various types of pericarditis and in the present patients the

noth: ECG patterns in penetrating wounds of heart 166

T waves are frequently tall and peaked during the first part of the early period
when RS-T elevation is present. These peaks tend to round off within a few
days, but inversion nearly always occurs later, after the R3-T elevation has
disappeared at the end of the second week or the early part of the third week

CASE 12 LEFT VENTR. WOUND

CASE 2 RT. VENTR. WOUND

Fig. 2.— Electrocardiograms in right and left ventricular Avounds illustrating preponderant influence

of pericarditis. ventricle. Note (a) recurrent acute pericarditis at thirty-one days

; with reversal of T-wave direction in standard leads: (b) so-called “late T, pattern at forty-five days,

fcl normal electrocardiogram at thirty months.

Ca?e 2 Stab wound of right ventricle. Note (a) diphasic T,, n at three days, suggesting non-
specific myocardial damage; (b) lack of localizing pattern, with inversion of T waves in all leads, char-
acteristic of pericarditis, at twenty-four days. ^

(see Figs. 1 and 2). In the present series the tracings of only six of twenty-one
patients with electrocardiograms taken during the first week show diphasic or
inverted T waves in leads other than III or Vi, whereas these changes are present
in twelve of thirteen patients with tracings taken during the third week. Among

734

AMERICAN HEART JOURNAL

ten patients with frequent electrocardiograms, inversions of T waves appear
between the eleventh and nineteenth days, averaging sixteen days. Their presence
during the first week is associated with clinical or other electrocardiographic evi-
dences of myocardial damage (Cases 1, 2, 5, S, 14, and 19).

A second consideration relating the abnormalities of the T waves to peri-
carditis is the tendency in various tjqDes of generalized pericarditis toward
widespread, more or less pensistent inversions of T waves. Of the present cases
suitable for anal>^is of this point, diphasic or inverted T waves are present in
eacli of the standard leads from the extremities in eight of fifteen cases and in
each precordial lead in five of ten cases. Thus in many cases the wide distribu-
tion seems to exclude localized myocardial damage, and the persistence and depth
of these inversions excludes nonspecific types of myocardial damage as the sole
or most important causes.

A third consideration is the presence in two patients (Fig. 1), without wounds
of the ventricles, of abnormalities of the T waves closely similar in the time of
their appearance, contour, and distribution to those seen in patients with wounds
of either ventricle (Fig. 2). Since the wounds did not involve the ventricles,
they cannot explain directly the abnormalities of the T waves. Nonspecific
ventricular myocardial damage incident to shock, anemia, or displacement of
the heart would not be as persistent. Exactly comparable changes are present in
“many cases of uncomplicated pericarditis of varied etiology. Therefore, peri-
carditis is the chief cause of these abnormalities in these two patients. The
similarity of the pattern to that seen in wounds of either ventricle (compare
Figs, 1 and 2) indicates the importance of pericarditis as a factor in the produc-
tion of the electrocardiographic findings in ventricular wounds.

Low voltage of the QR.S complexes of the standard leads from the e.xtremitics
is present in six patients. This change is consistent with, though not pathog-
nomonic of, pericarditis.

Localizing Findings.- -

Right Ventricular Wounds: Five patients (Cases 1 to 5) were found at
operation to have wounds of the right ventricle. The electrocardiograms of two
patient.s show definite evidences of localized right ventricular myocardial damage
ns illustrated in Fig. 3 and described in the legend. One factor complicating
the interpretation in Case 5 is the pre.cence at autopsy of chronic rheumatic heart
disease with mitral stenosis and insufficiency and right ventricular hypertrophy.
However, the heart weighed only 410 grams and there was a small hemorrhagic
f.xtrtivasaiion in the interventricular septum which, along witJi the wounds of
the right ventricle, seems to be a better explanation of the right bundle branch
Idock. I'urthermorc, right ventricular hypertrophy would not explain the R-T
segment elevations which arc most marked in the precordial leads over the right
ventricle. In one patient (Case 1) there was coincidental asymptomatic hyper-
teufive cardiova.-cular disease with moderate left ventricular hypertrophy and
prob.ahly ah.n s>-philitic aortitis. However, localized myocardial damage as
indir«"!t>dl>y the T-wavechange.« in I^-adVt-\'i which arc not present in I..cad ¥«

NOTH: ECG PATTERNS IN PENETRATING WOUNDS OF HEART 735

would be very unusual in either of these two conditions. Also, the equal ampli-
tude of the R and S waves in Lead Vi indicate that the precordial electrode was
near the interventricular septum. This corresponds with the location of the
wound in the right Ventricle near the septum.

Two additional patients in this group have questionable localizing findings.
Pertinent tracings are shown in Fig. 4. Case 3 with a “T2, T3 pattern” is
considered questionable because of the fact that pericarditis may cause inversions
of T waves at this time and in these leads alone (vide infra). However, the nurn-
ber of reported cases of right ventricular wounds with persistence of this pattern
beyond a three-month period indicates that this may be valid as a localizing

, CASE U

Fig. 3. — Definite localizing patterns in right ventricular vounds.

Case 5. Incomplete right bundle branch block: elevation R-Tvs, 4, indicating localized subepicardial
process.

Case 1. Note (a) late localized T-wavo changes in Vj-Vb corre-sponding to location of vround at left
border of right ventricle; (b) incomplete right bundle branch block; (c) left ventricular preponderance
due to associated hypertensive cardiovascular disease.

pattern in some instances. The evidence of localized damage in Case 4 is ad-
mittedly slender, and the observed elevations of the R-T segments in Lead V2
on the fifteenth day could be dependent upon the high voltage of the QRS
complex. However, they do suggest a localized subepicardial process. In the
final patient (Case 2 — Fig. 2), the electrocardiographic abnormalities are attribut-
able to pericarditis.

Left Ventricular Wounds-. There are eleven patients in whom left ventricular
wounds were discovered at operation. In six definite electrocardiographic"
findings of left ventricular damage thought to be due to the wound are present.
Electrocardiograms in two of these patients with known or probable injury to
the left coronary’- artery are shown in Fig. 5. Itds possible that in the second
(Case 6) the diminished R waves are due to the wound itself. However, if this

CASE 4

fit:, — /'<‘T Irpffii;, fr^ opp-i.tiie paoe.

noth; egg patterns in PENETEATING wounds of heart * 737

were so, one would expect Q patterns or their equivalents in more of the cases
with multiple precordial leads. The infrequency of this finding as well as the
fact that the wound was very close to the left coronary artery makes it probable
that this vessel was occluded, resulting in an anteroapical myocardial infarct.
In both of these cases the pattern of anterior infarction gives indirect evidence
of the location of the wound in the region of the left coronary artery.

v- ' / . I- i i" V ' ‘ i j-"

' Pr«-Ar^

CASE is ~ “■

CASE 6

Fig. 5. — Left ventricular Avounds with known or probable injury to left coronary artery.

Case 15. Patient found to have laceration of left ventricle dividing descending branch of left
coronary artery. Note Q pattern, marked R-T elevation characteristic of recent anterior infarct.
Unusual degree of elevation probably partly due to hemopericardium.

Case 6 . Wound 3 to 4 mm. from left coronary artery; attempt made to avoid its suture. Note
(a) very small R waves in V 4 probably due to anterior infarction, possibly to wounditself; (b) regression
of T-wave inversions, persistently small R waves at three years.

Four of the six patients with left ventricular wounds with definite localizing
findings have T-wave changes in Leads I and II and in the precordial leads over the
left ventricle. Fig. 6 illustrates three such cases. Each of these young men was
re-examined completely b}'^ me at the time of the last recorded electrocardiogram,
and hypertension, valvular lesions, and left ventricular enlargement were ex-
cluded. Furthermore, the precordial leads do not show left ventricular hyper-

Fig. 4 . — Right ventricular wounds with questionable locali7ing signs.

Case 3. Note preponderant inversion of Tj, 3 persisting through the forty-seventh day, the so-
called ‘'T 2 , T 3 pattern."

Case. 4. Note (a) isolated elevation of R-T segment in Vj on fifteenth and twenty-third day, sug-
gesting localized subenicardial process in right ventricle: (b) presence of so-calRd “late Ti" pattern on
twenty-third day, here associated with a right instead of a left ventricular wound and probably due to '
subacute stage of pericarditis.

73S

AMERICAN HEART JOURNAI,

' " I" V, Va Vj Vg Vg

I i4. C I/, ft %.'n!ric!!lar wiiunrU with Jorani-inp T-wavo jiatt* nis

r^n'h! <I.vr-a«; rml.fr l\-J ^.-riZml aw" mj emuour m|Rpestinp rnjo-

''r*i r^nrif^ " " at ek'ht months c*xci^pt vrido KplUtln#: of

I Srf 'm Ibmf aln^rr"'"’'"'' "* '"O"'’-- *« orHymptom,

NOTH: ECO PATTERNS IN PENETRA.TING WOUNDS OF HEART 739

trophy, since the time intervals from the initial QRS deflections to the peak
of the R waves are 0.04 second or less in the leads over the left ventricle. For
these reasons it may be assumed safely that coincidental cardiac disease is not a
factor. Inspection of Table IV reveals that T-wave inversions in Cases 10 and 14
were present also in a number of earlier tracings during the first and second
months. The difficulty in interpreting these earlier T-wave changes as due to
localized left ventricular injury is shown by the fact that each of the three
patients with right ventricular wounds (including Case 2— Fig. 2, and Case 4—
Fig! 4) with tracings during this intermediate period showed abnormalities in the
same leads.

When the T waves are as deep at any time as those in Case 8 of Fig. 6,
localized damage may be assumed to be present since pericarditis alone rarely
produces such T waves. The T-wave inversions occurring during the first week
may indicate localized ventricular injury since pericarditis rarely causes inver-
sions at this time, particularly if elevation of the R-T segment is present con-
currently. However, nonspecific types of myocardial damage incident to shock,
anemia, or the operative procedure may produce similar changes during this
period, and so, again, it is unsafe to consider them as localizing findings.

The same considerations regarding the persistence of effects of pericarditis
apply to the significance of the disappearance of abnormalities of the T waves
in certain precordial leads while they are still present in others (see Case 6 —
Fig. 5). This may be due to the subsidence of the generalized pericarditis and
perhaps should be so considered in most cases with tracings during the first
' two or three months. However, it is probable that in some of these tracings this'
represents a diminution in the size of the injured area. When it is large, it may
affect the T waves in leads taken over the opposite ventricle, as is commonly
seen in leads over the right ventricle in instances of anteroseptal infarcts of the
left ventricle due to coronary heart disease.

Case 12 (Fig. 2) is considered to show questionable localizing findings since
the last abnormal electrocardiogram showing limitation of T-wave abnormalities
to Leads I and IVF is taken at forty-five days, during a period when pericarditis
could still be exerting its-effects. Of the four patients without localizing changes;
two (Cases 9 and 16) had only one or a few electrocardiograms, and these were
taken during the first week, and the other two (Cases 7 and 11) had tracings
only during the first month. All showed typical changes of pericarditis.

Wounds Not Involving the Ventricles: The electrocardiograms of the two
patients with wounds not involving the ventricles are shown in Fig. 1. In a
•patient with a left auricular wound (Case 18), the only localizing finding is notch-
ing of the P waves in Leads I and 11. This is considered to be of questionable
localizing significance because it is not marked enough to be definitely abnormal.

Wounds in Patients Without Operation : Two of the five patients have elec-
trocardiograms with definite localizing findings (Cases 19 and 20 — Fig. 7). Both
T and Q patterns are present. The presence of Q waves raises the question of
whether the coronary arteries were involved in the lacerations. In Case 19
the existence of a cardiac wound was not suspected until the electrocardiogram

\MERICAX HEART JOURN'Al

CASE

20

' ,-. I; /

11 III

\

•.' -m

CASE 19

CASE 2!

Vhi. 7. — f;i>'ctroranli(n:r,Mti» In «itlioui o|«Taiion.

wavt. r.rnl drvpS.v Itivmwl T «nv,- in l^-ad IV ^•ln(licatIvcM.ItlH.rofalaceratIonortllf.

- - vcntncuu.

! ‘ !'’■ tall T avavi's in iin>cor<lial leads at nrtv iw,.

a tt,a^ fcnif'-.r ^ ‘ ^ coronary arterj . ( Patient was stabbed In tho back with

mh^'Z^L snbepicantial tnyocardlal process localir.ed over

NOTH : ECG PATTERNS IN PENETRATING WOUNDS OF HEART 741

was obtained. This patient, a Negro 26 years of age, was stabbed in the back
with a long knife in two places, both between the levels of the second. and fifth
dorsal vertebrae, with resulting left-sided hemopneumothorax. The initial
period of shcck was short, the degree of anemia only moderate, and the Kline
test of the blood serum for syphilis negative. There were no symptoms or
findings of cardiac failure. Cardiac examination revealed a pericardial rub on
the second day and a rcentgencgram showed slight cardiac enlargement. At
first there was displacement of the mediastinum to the right, but this and the
pleural effusion had practically disappeared by the eighteenth day. The well-
marked Q and T patterns in Leads II and III may have been due m.erely to the
wound of the posterior basal portion of the left ventricle, but in spite of the un-
eventful clinical course it is suspected that the right coronary artery was lacerated
with the resulting electrocardiographic findings’ which are classical for an infarct
in this area.

The other patient (Case 20), a Negro 27 years of age, presented an oblique
laceration two inches long in the third left intercostal space near the mid-
clavicular line, with resulting left hemopneumothorax. The postoperative
course was stormy with tachycardia and dyspnea. The same considerations
apply to the question of laceration of a coronary artery in this case as in the one
just discussed.

A third case (Case 21 — Fig. 7) shows elevation of the R-T segments in Leads
Vi and V 2 only, which is regarded as suggestive evidence of early subepicardial
myocardial damage over the right ventricle. There are no localizing findings
in the remaining two cases.

Follow-up Studies. — ^The purpose of this part of the study was threefold :
first, to obtain electrccardicgrams at a late enough date to avoid the complicat-
ing patterns of pericarditis; second, to attempt to correlate the electrocardio-
graphic findings with other evidence bearing upon the cardiac status of these
patients; and third, to look for evidences of constrictive pericarditis. The first
aspect , of this study has been incorporated into the preceding discussion, but
these late electrocardiographic findings are listed in Table V for comparison with
Tables II and III.

The symptoms and physical, roentgenologic, and electrocardiographic
findings in eight patients examined by me at periods varying between five and
thirty-six months following a cardiac wound are shown in Table VI. It is
notable that in the first three cases with normal electrocardiograms all other
objective findings are likewise entirely normal. However, all of these patients
have symptoms. None of these are clearly of cardiac origin, and in each case
there are unmistakable evidences of neurosis. The remaining five patients have
abnormal electrocardiograms. In three of these other definite objective evi-
dences of cardiac damage are present. In two the only other objective abnor-
mality is the fluoroscopic finding of apical pleuropericardial adhesions not ex-
tensive enough to be clinically significant. Thus in the cases of these, two
patients the electrocardiographic findings are the only definite evidence of resi- ,
dual cardiac damage. In Case 1 the physical and roentgen findings are probably

TAfii.K VI. Findings in Foi.i.ow-ifP Siudiks of Eight Patiknis

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744

AMERICAN HEART JOURNAE

due chiefly to the associated hypertensive heart disease, whereas the electro-
cardiogram shows the efTect of this complication and also of the right ventricular
damage caused by the wound. While two of these five patients presented symp-
toms which were hard to evaluate, both exhibited abnormal objective findings in
addition to the electrocardiogram. Evidences of chronic adhesive pericarditis •
suflicient to cau.se systolic retraction of ribs, fi.xation of the heart, or pulsus
paradoxus were not observed, and the venous pressure in the antecubital vein
was found to be normal in the seven patients tested.

COMMENT

KitvjEW ANu Discussion ok the Electrocardiographic Findings at
\^ tRious Stages. —

Jiarly Stage {Preoperaiive and First Twenty-Jour Ilotirs ). — The findings among
the thirty-one cases depicted in the literature are described in detail in the fore-
going and are summarized in Table I. The findings among eight cases in the
present serie.': arc presented in the description of the RS-T segment patterns of
pericarditis, in Table IV, and are illustrated in Figs. 1 and 5. Combining the
iwo scries, there were nine patients with preoperati\'e tracings. Three showed
definite evidence of an anterior myocardial infarct; one, right bundle branch
block; one, definite pericarditis; two, suggestive pericarditis; and one, nonspecific
changes: one was normal. The findings in these cases have (he most direct
hearing upon the question of the value of the electrocardiogram in the preoperative
diagnosis of cardiac involvement in a thoracic wound. They indicate that definite
evidences of cardiac involvement may be found in a sizeable proportion of such
ca.^es but that occasionally normal or nonspecific patterns may occur. From
the standpoint of operative criteria, the physical and fluoroscopic e\'idences of
cardiac tamponade are more directly applicable.

In the combined total of thirty-nine patients with one or more (racings taken
preoperatively and ’’or during the first twenty-four hours, the electro cardiograms
were diagnostic of the presence of myocardial infarction, bundle branch block,
or pericarditis in twenty-one instances and suggesti\e of one rf these conditions
in an additional nine instances. However, in spite of the fact that it is at this
stage that shock, anemia, and displacements of the heart are most prominent
and are added to the direct effects of the wound, there were fi\-e instances in
which the elcclrocartliogram was essentially normal. In eight patients, including
some with suggestions of other lesions, nonspecific abnormalities were present.
In several instances when the first electrocardiogram was taken preoperatively
or within a few minutc»s or hour.-, following operation, .subsequent tracings during
the fir.-t twenty-four hour.s showed the appearance of evidcnce.s of perirarditis
or infarctitm. Since shock, anemia, and displacements of the heart may occur in
wounds of the thorax not involving the heart and may cause nonspecific elect ro-
catdit'gfapluc abnormalities including inver.--ion.s of the T waves, these early
elfclrocardiugrams should be nmsidered a.s indicating cardiac involv’^ement only
ttln n piltim^of infarctimi. bundle branch block, or acute pericarditis are present.

NOTH : ECG PATTERNS IN PENETRATING WOUNDS OF HEART 745

The first two of these patterns also provide information as to the site of the cardiac
wound.

Early Intermediate Stage (^Seco7id Day Through the First Three Weeks ). —
The description by Herve and Forero Sarabia of the series of events taking place
during this period is given in the foregoing and adequately covers the charac-
teristic RS-T and T wave patterns as seen in tracings depicted in the literature.
The findings in the present series are very similar, and since they are predomin-
antly those of pericarditis, they are described under that section. Reference
to Table IV and to Figs. 1, 2, 4, and 7 will disclose the details as seen in individual
cases in the present series. The general uniformity of the patterns is due to the
practically universal presence of pericarditis which produces very characteristic
changes at this stage. Thus, the patterns are usually similar regardless of the
location of the wound. The exceptions are instances.of right bundle branch block,
as illustrated by Case 5 of Fig. 3, and also instances of laceration or ligation of a
coronary artery with resultant myocardial infarction. However, during the
first few days of the early intermediate period, the characteristic reciprocal de-
pression of the RS-T segment in Lead III occurring with anterior infarction usually
disappears due to the opposing effect of the pericarditis which tends to' cause
elevation in all leads. This same sequence of effects has been observed in ex-
perin'>ental myocardial infarction^ and in clinical instances of coronary heart
disease with myocardial infarction complicated by pericarditis.^ The second,
distinctive feature in the cases with complicating infarction is the presence of
abnormal Q waves. They tend to remain for months or years and so may occur
at any of the stages being considered. The rare occurrence of the Q2-Q3 pattern
of the posterior infarction in a cardiac wound is shown in Case 19 of Fig. 7.
Esophageal and unipolar leads from the extremities would have contributed
valuable confirmatory evidence in this case. In anterior infarcts, the pathologic
Q waves are best seen in the precordial leads. Case 15 (Fig. 5) is the only anatom-
ically proved instance of myocardial infarction in the present series, although it
. is likely that Case 6 of Fig. 5, and Case 20 of Fig. 7 are additional instances of
anterior infarction. The alternate explanation of these Q- or diminished R-wave
patterns is that they are due to the effects of a wound which involves nearly all
or the complete thickness of the ventricular wall in the region underlying the
exploring electrode. As mentioned previously, if the wound itself caused the
Q waves, they might be expected to appear more frequently, especially when
multiple precordial leads are taken. In either event they represent a localizing
effect of the wound. The absence of Q waves in the precordial leads in instances
described in the literature in which ligation of the left coronary artery'^ or its
branches is known to have occurred is explained either by the infarct’s not ex-'
tending through the full thickness of the wall or being localized to an area not
influencing the single precordial electrode employed. The idea that more ade-
quate collateral circulation exists in hearts with previously normal coronary arter-
ies and that therefore infarction may not occur has been proved to be false by the
studies of Blumgart and co-workers.^®

In the first part of the early intermediate period, inversions of the T waves
cannot be ascribed to pericarditis since it is known that they almost always

746

AiMERICAN heart journal

appear later in uncomplicated instances of this condition. Neither can they be
considered as a direct effect of the cardiac wound since there is no discoverable
relation between the leads in which they occur and the location of the wound.
Tliey are best considered as evidences of nonspecific myocardial damage and
are probably often due to shock and anemia which are most marked at this stage.
Occurrence of very deep T waves, such as those seen in the eighteenth day in
Case 8 of Fig, 6, suggest myocardial damage rather than pericarditis because the
latter is less often responsible for inversions of this depth.

Late Jvlcrmediafe Stage {Three Weeks Through Three Months ). — The point
of greatest interest concerning the late intermediate stage is whether or not the
effects of pericarditis disappear sufficiently so that patterns due to the cardiac
vvound itself can be recognized. As previously mentioned, the opinion has been
e.vpressed**’''^ that this is possible after the second week. However, a review of
the literature on the persistence of the effects of pericarditis of various other types
does not support this opinion. Thus, Winternitz and LangendorF® stated that the
T waves usually became in\erted during the third week and that the inversion
might last for several months, although this abnormality always disappeared
later when healing had occurred. Holzmann,"' in classifying the electrocardio-
graphic cJjanges during pericarditis, placed the “late acute phase” between the
tenth day and the sixth week, the subacute stage between six weeks and two
months. Perhaps the best idea of hotv long the electrocardiographic effects
of the type of pericarditis accompanying cardiac wounds may persist is gained
from a review of ca.scs of atrial or pericardial wounds in which the persistent
T-wave inversions are necessarily associated with the pericarditis, since these
.‘itruclure.s have no direct effect on the T waves. 7'here are five cases'’'’'”*® (CASe.s
. mjitablc for this purpose depicted in the literature. T-wave abnormalities
are still present at forty-three, fifty-two, sixty, sixty, and ninety days. In two
similar cases in the present series, abnormalities are present in the last electro-
c.;irdiograms at twenty-four and ninety-seven days (Fig. 1).

I'here is some additional cHdence for the pcrsi.stence of the effects of peri-
carditis during this period. In Case 12 of Fig. 2 the reversal from negative to
po.c;tti\'c of the T wa\'e in Lead I and the reappearance of elevation of the RS-T
segment in Lead IVF in tlie tracing taken on the thirty-first day are character-
istic of an acute flare-up of pericarditis. This makes it hazardous to consider
the next tracing in this same case taken only fourteen days later which conforms
to the so-called “late Tj pattern” of left ventricular wounds as definitely due
lo the localized effect of the wound rather than to subacute pericarditis. The
cloH' simil.arity l>eiween the tracing at nventy-six daj-s in this case to that of
twciuy-four days in Case 2 of Fig. 2 and that of tAventy-three daj-s in Case 4
of Fig. 4, Ixnh of the latter two occurring in wounds of the right ventricle, further
iiftistrates the difficulties of ascribing localizing significance to changes in the
'r w.ives during this period. Case ,4 of Fig. 4 illustrates the so-called “late T;-T.-t
pattern” of right ventricular wounds. While it is true that many types of right
vcKiricular myocardial damage are reflected in these leads, it is also true that
unronjpHr.Uec! pericarditis may cau=e inversions of the T wa\'es in the.«e leads

noth: ecg patterns in penetrating wounds of heart 747

alone.®® Since it has been shown that pericarditis is frequently still active,
it, is doubted that such a pattern should be considered at this time as definitely
due to the direct effect of the right ventricular wound.

Late Stage {Three Months or More After the Wound ). — Excluding patients
with complicating myocardial infarction, the three standard leads in approxi-
matety 50 per cent of patients with persistently abnormal tracings (Tables II
and V) correspond very well with the previously described “late Ti pattern”
of left ventricular wounds and in most instances with the “late T2-T3 pattern”
of right ventricular wounds. In the former the T wave in Lead I was always
abnormal, whereas combined abnormalities of the T waves in Leads II and III
did not occur. In the right ventricular wounds only one case showed T-wave
abnormalities limited to Lead I, whereas the remaining cases showed either the
T2-T3 pattern or right bundle branch block. This correspondence with the
previously described T-wave patterns which were based upon electrocardiograms
taken at periods from two weeks onward suggests that these patterns may appear
earlier than three months. However, they are not as reliable then as later.

Among the cases depicted in the literature with a single precordial lead,
there was only one patient in whom it was entirely normal. In two patients it
constituted the chief although not the only abnormality. Its T wave was in-
verted in both right and left ventricular wounds as might be expected from its
location, which usually overlies the vicinity of the interventricular septum and
so exposes it to influences from either ventricle. For this reason and also because
from experience in other diseases of the heart it is known that a single precardial
lead may not record some right ventricular or lateral left ventricular lesions,
multiple precordial leads would be expected to be superior in detecting small
lesions and in indicating the location of the wound. This appears to be so as
judged by the findings in these leads in the present series of patients. All of the
patients with left ventricular wounds with persistently abnormal tracings showed
abnormal T waves in Lead Ve, and all but one had abnormal T waves in Lead W,
but there were three patients in whom this deflection was normal in Lead V4.
Since the location of this lead is the same as that usually chosen for a single
precordial lead, the evidences of myocardial damage in these patients would have
been missed by such a lead. While there was onl}'^ one patient with a right ven-
tricular wound in whom the tracings were abnormal at this stage, the T wave
in Lead Vg was upright and the maximum inversion occurred in Lead V4, which
corresponded to the location of the wound in the right ventricle near the septum.

Until these late tracings were obtained, there seemed to be some question as
to whether the wound itself, in the absence of damage to a coronary artery or to
the branches of the bundle of His, caused any detectable electrocardiographic
changes. However, the later emergence of these patterns indicates that they
were present earlier but usually indistinguishable from the changes due to peri-
carditis.

Follow-up Stutdies in Cardiac Wounds. — ^Apart from the electrocardio-
graphic findings, no attempt has been made to review the literature concerning the

748

AMERICAN HEART JOURNAL

}aic results of penetrating cardiac wounds. As mentioned previously, there have
been only thirteen cases with published electrocardiograms followed for more than
six months. The most extensive study of late electrocardiographic and other
clinical findings is that of Steffens,'^ although in it the electrocardiograms are
not published. His 109 patients were German \'eterans of World W ar I who
had sustained bullet wounds from ten to twenty years before re-e.xamination.
In only ten of the sixty-nine cases studied electrocardiographically with the
standard leads from the extremities were the tracings abnormal. In several
of these patients there was complicating disease of the heart sufficient to account
for the abnormalities. In the remaining patients there were no other objective
evidences of myocardial damage. Of the whole group, however, only 13 per
cent had no complaint.s. For the most part, the symptoms were considered as
psychogenic.

In the present study also the electrocardiograms exhibited the most constant
and per.^^islent objective abnormality. Because of this they are of value in
indicating the need for some caution in the management of such cases, although
the patient’s symptoms and physical and roentgen findings must also be con-
sidered. In patients who have indefinite symptoms of a type suggesting a psy-
choncurosi.s, but whose physical and roentgen examinations disclose no abnor-
malities, the finding of a normal electrocardiogram, particularly when multiple
prccordial leads are taken, is strong evidence in favor of the functional origin
of the complaints. It indicates the' prime necessity of ps\'chotherapy in their
management.

SU.MMAUY ANTJ CONCI.USIONS

1 . A review of the literature on the electrocardiogram in penetrating wounds
rtf the heart is pro.sented including a tabular summary of thirty-one cases in
which tracing.^ were obtained during the first twenty-four hours and of an equal
number in which they were taken three months or more (average, 7.1 months)
after the wound,

2. 7'he electrocardir)graphic findings in twenty-three similar cases observed
at Detroit Reajiving Hospital are described and illustrative examples presented.
In sixtcNm of these case.s. multiple precordial leads were obtained and in tweh'e
the follow-up period was three month.s or longer (average, 18.5 months). Eight
patients were completely re-examined by me at periods \-arying between fi\ e and
thiriy-.«ix month.s (average, 19.1 months) following the wound, thus making
pj.-’sible a correIatif)n of the symptoms and physical and roentgenologic findings
with the electrocardiograms at this late .‘^tage.

3. in the pre.'^ent stTie.s of twenty-three patients, definite electrocardio-
graphic evidences of pericanlitis appeared in seventeen, in seven of ivhom no
other abnormalities could be detected. Definite localizing patterns directly
attributable to the wound were pre.H‘ni in ten. In fi\e of these the localizing
fintlirig'^ api>earc<I in early eleclrorardifjgrams and con.sisied of right bundle
b-.uiclj block (one ca.<e) nr Q-wave pattern.^ due either to complicating myo-

noth: ecg patterns in penetrating, wounds of heart 749

cardkl infarction from injury of a coronary artery or possibly in some instances
to involvement of the full thickness of the ventricular wall by the wound
itself. In the other five cases the localizing patterns were not well-defined until
three months or more after the wound. Four of these were instances of left
ventricular wounds characterized by abnormalities of the T waves in Lead I
and in one or more of the precordial Leads V 4 , Vs, and Vs. The one instance of
a right ventricular wound in which a late tracing was obtained showed abnor-
malities of the T waves in Leads V3, V 4 , and Vs, corresponding closely with the
location of the wound in the right ventricle near the septum.

4. The clinical follow-up studies on eight patients in the present series
indicates that the electrocardiogram exhibits the most persistent objective
abnormalities. When present, they suggest the need for some caution in the
management of the patient. When the electrocardiogram is normal in all leads,
including those taken from multiple precordial stations, it is of aid in confirming
the psychogenic origin of persistent subjective symptoms.

As judged by the findings in the present series and in those in which the
electrocardiograms are depicted in the literature, the following conclusions are
drawn :

1. Preoperative electrocardiograms show definite evidences of cardiac
involvement in the majority of cases and therefore may aid in the decision as to
whether or not the heart is included in a thoracic wound. Electrocardiographic
findings such as those of pericarditis, bundle branch block, or myocardial in-
farction may be accepted as definite evidences of cardiac involvement, whereas
T-wave abnormalities and minor deviations of the RS-T segments cannot be
relied upon since they could be caused by shock, anemia, or displacements of the
heart which are often present in thoracic wounds without cardiac involvement.

2. During the first twenty-four hours the incidence of abnormal tracings
increases. Changes due to pericarditis frequently appear but usuallj'^ at this
time do not obscure the RS-T segment and T-wave patterns of myocardial in-

, farction due to laceration or ligation of a coronary artery.

3. During the early intermediate period (second day through the first
three weeks) the effects of pericarditis predominate and cause strikingly similar
findings in the majority of the cases regardless of the location of the wound.
The RS-T segment and T-wave changes of anterior myocardial infarction like-
wise may be obscured, although a sufficient number of precordial leads would be
expected to show Q waves in most of such cases.

4. During the late intermediate period (three weeks through three months)
the electrocardiographic effects of pericarditis may persist. This makes the
T-wave patterns unreliable at this time for locating the site of the wound. In
this period and in all of the previous periods localizing findings are provided chiefly
by either bundle branch block or indirectly by Q-wave patterns of infarction.

5. The consistent finding of abnormalities of the T waves limited to one or
more of the precordial Leads AT, V5, and Ve in late tracings of patients with left
ventricular wounds amplifies the previously described “Ti pattern” and demon-

75 **

AMERICAN’ HEART JOURNAL

birates tlie superiority of such leads over a single precordial lead. The 'late
tracing of one patient with a wound of the right ventricle, as well as clinical ex-
perience with multiple precordial leads in other right ventricular lesions, suggests
that such leads may be expected to jdeld information not afforded by a single
precordial lead and should amplify the previously described “T^ pattern.”

6. The failure to find differences in the electrocardiographic patterns result-
ing from wounds of different parts of the heart or between those with and with-
out interruption of a sizeable coronary arterj’ is usually due to the obscuring effects
of pericarditis in most tracings except those taken either ver>’ early or after
.several months have elap.sed. It may also be due to an insufficient number of
leads or to not recognizing the distinctions between patterns of pericarditis and
myocardial infarction.

7. Further investigation is needed to clarify two interesting questions raised
by the findings in multiple precordial leads in the present study: (A) May the
wound itself produce Q waves in one or mere of these leads, or are these always
<iue to an area of myocardial infarction from interruption of a coronarj'^ arlerjL?
(B) Is the progres.sive disappearance of inversion of the T waves in some of the
precordial leads entirely due to the recession of generalized pericarditis, or may it
be due partly to a decrease in the size of the wound and thus give valuable evi-
dence of the healing process?

Tlic author wishes to express his tiianks to Dr. Morris H. Blau and other members of the
SurRicnl Department for their help and cooperation in this study. Also he wishes to thank Dr.
f tordon B. Mycr.s for helpful advice and criticism.

REFERENCES

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B. Davenport. G. L.: Suture of Wound of the Hc.art, J. A. M. A. 02: 1840, 1924.

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Stab Wound of the He.rrt. J. Thoracic Surg. 5: 208, 1935.

SO. Davcnivsrt, G. L., and .Markic, FL: The Electrocardiogram in Stab Wounds of the Heart;
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1 1 Eakin. W. W.: The Removal of a Gorge Needle From the Heart With Electrocardiographic
CTyiges in Rhythm During Operation, .Am. Hr, set J. 8: 540, 1933,

12, Fraser. W. .A., and Tevon. M.; Electrocardiographic Finrlings .As.^ociated With a Gunshot
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1. ^. Gd*c-.!iv. W. I.: Cirdi.ic Tanif>;inadc; Report of a Stab Wound in the Right Ventricle,

7i*iL S’.jrgesn 97: 2S?, 1944.

54 Gb ane, W.. .aiul Schulenfierg, B.: A Penetrating .Stab Wound of the Heart; Operation;
Recovery, Ginret 2: 172, 19.77.

noth; ecg patterns in penetrating wounds of heart 751

15. Glasser,.S. T., Mersheimer, W. L., and Shiner, L: Bullet Wound of Left Cardiac Auricle

With Suture and Recovery; Review of Literature, Am. J. Surg. 53; 131, 1941.

16. Goldberger, H. A., and Clark, H. E.: Migration of Needle Into Heart Through Chest Wall:

Surgical Removal: Electrocardiographic and Roentgenographic Studies, T. A. M. A.
105: 193,1935.

17. Herfarth, H.: Beitrag zur Herzchirurgie (unter besonderer Beriicksichtigung des Ekg),

Zentralbl. f. Chir. 67: 2110, 1940.

18. Hyman, A. S., and Fisher, J. L.: Post-Traumatic Disturbances of the Heart, Am. Heart

J. 2: 61, 1926.

19. Kouck^', J. D., and Milles, G.: Stab Wounds of the Heart, Arch. Int. Med. 56; 281, 1935.

20. Linner, B.: Verletzungen des Herzens durch Nadeln, Zentralbl. f. Chir. 68: 208, 1941.

21. Merkel, H.: Durch Herznaht geheilte Stichverletzung des Herzens, Zentralbl. f. Chir.

66: 2323, 1939.

22. Mohr, H.: Spatfolgen einer Herznaht mit Un'terbindung des Ramus descendens der Arteria

coronaria sinistra, Zentralbl. f. Chir. 68: 11, 1941.

23. Mondry, F.: Das Elektrokardiogramm bei mehrfacher Herzstichverletzung, Zentralbl. f.

Chir. 66; 743, 1939.

24. Nana, A.: Penetrierende operierte Herzwunde; Spatresultate, Zentralbl. f. Chir. 66: 2198,

1939.

25. Olin, C. B., and Hughes, J. D.: Stab Wound of the Heart With Coronary Ligation, J.

Thoracic Surg. 9; 99, 1939.

26. Peitmann; Ueber Arbeitsfahigkeit nach Herznaht, Miinchen. med. Wchnschr. 86; 604,

1939.

27. Purks, W. K.: The Electrocardiographic Findings Following Ligation of Decending Branch

of the Left Coronary' Arterj' in Man, .A.M. Heart J. 7 :101, 1931.

28. Ramsdell, E. G.: Stab Wounds of the Heart, Ann. Surg. 99:141, 1934.

29. Schlomka, G.: Elektrokardiographische Beobachtungen bei Herzstichverletzung, Deutsche

med. Wchnschr. 57 : 630, 1931.

30. Schwab, E. H., and Herrmann, G.: Alterations of the Electrocardiogram in Diseases of the

Pericardium, Arch. Int. Med. 55: 917, 1935.

31. Solovay, J., Rice, G. D., and Solpvay, H. V.: Electrocardiographic Changes in Stab and

Gunshot Wounds of the Heart, With Review of Literature, Ann. Int. Med. 15: 465,
1941.

32. VanderVeer, J. B., and Norris, R. F.: The Electrocardiographic Changes in Acute Peri-

carditis; Clinical and Pathological Study, Am. Heart J. 14; 31, 1937.

33. Warthen, H. J.: Stab Wound of the Heart; Report of Case, Ann. Surg. 102; 147, 1935.

34. Weinstein, M.; Stab Wound of the Heart; Report of a Successful Operation, J. A. M. A.

122; 664, 1943.

35. Zerbini, E. de J.: Coronary Ligation in Wounds of the Heart, J. Thoracic Surg. 12: 642,

1943.

36. Abramson, P. D.: Stab Wound of the Heart, New Orleans M & S. J. 86: 376, 1933.

37. Angeli: Quoted by Solpvay and others.®^

38. Bruckner, J. D.: Stab Wound of the Heart; Case Report of Successful Suture, Ann. Surg.

118; 46, 1943.

39. Clark, J. F.: Suture of Stab Wound of the Heart; Report of Case, Texas State J. Med.

29; 203, 1933.

40. Fischer, L.: Herz^'erletzung und Elecktrokardiogramm, Arch. f. klin. Chir. 188: 557, 1937.

41. Flaum, E.: Ueber d>e Bedeutung den Koronarveranderungen des Menschlichen Elektro-

kardipgramms, Wein. Arch. f. inn. Med. 23; 409, 1933.

42. , Holubee: Quoted by Wood.'®

43. Junghans, H.: Zur Frage der Leistungsfahigkeit nach operativ behandelten Herzverlet-

zungen, Zentralbl. f. Chir. 67: 2257, 1940.

44. Kienle; Quoted by Solovay and others.'^

45. Kment: Quoted bj' Oppolzer.^®

46. Matti: Quoted by Solovay and others.®*

47. Morris, K. A.: Penetrating Wpunds of the Heart, Am. J. Surg. 41: 108, 1938.

48. Oppolzer,' R.: Heilung eines Herzdprchschusses mit Durchtrennung des Hinteren abstei-

genden Astes der rechten Coronararterie nebst elektrokardiographischer Verfolgung,
Deutsche Ztschr. f. Chir. 242; 620, 1934.

49. Rehn: Quoted by Oppolzer.^'

50. Scherf: Quoted by Oppolzer .‘’®

51. Schroder, C. H.: Naht einer zAveifachen Stichverletzung des Herzens, Zentralbl. f. Chir.

67: 2345, 1940.

52. Williams, D. B. Successful Suture of Stab Wound of the Heart, Nehv Orleans M. & S. J.

95; 470, 1943.

53. Herve, L., and Forero Sarabia, A.: Estudio electrocardiografico de 30 heridas del corazon

y del pericardio, Medicina, Buenos Aires 3: 387, 1943.

752

AMERICAN HEART JOURNAL

55,

56,

57,

3S.

59.

60 .

61.

62.

6 . 1 .

6 -?.

65.

66 .

67.

68 .

69.

70.

71.

73.

73.

74.

McGuire. J.. and McGrath, E. J.: Penetrating and Lacerating Wounds of the Heart, Tr.
A. Am. Phvsicians .56; 194, 1941.

Elkin, D. C., and' Phillins, H. S.; Stab Wound of the Heart; Electrocardiographic Studies
nf Two Cases. J. Thoracic Surg. 1; 113. 1931.

P.iradc, G. W., and Rating, B.: Beitrage zuni Problem dcr Herzverletzung, Klin, ^^■ch^schr.

19: 1276. 1940.

Porter. W, B.. and Bigger. I. A.: Nonfatal Stab Wounds of the Ventricles, With Electro-
cardiographic Signs of Coronary
M.Sc. lai; 799,' 1932.

Wcinternitz, M.. and Langcndorf, R.:

med. Srandinav. 91; 141, 1938.
Blalock. ,A., and flavitch, M. M.: A

Thrombosis and Absence of Anginal Pain, Am, J.
Das Elektrokardiogramm der Perikarditis, Acta

Consideration of the Non-Operative Treatment of
Cardiac Tamponade Resulting From Wounds of the Heart, Surgery II: 157, 1943.
Bland, E. F.: Foreign Bodies in and About the Heart, Am. He.\kt J. 27; 5S8, 1944.
Gnrrcton S^h^a, A., Herve, L. L, and Fuenzalida. C. O.t Estudio electrocardirgrafico cn
dos intcrvenciones quirurgeas por heridas del corazon, Rev. med. de Chile 70: 793,

1942.

Linder, H., and Hodo, H.: Stab Wounds of the Heart and Pericardium, South. M. J. .37:
261, 1944.

Nissen, R.: Advances in Heart Surgerj', J. internat. Coll. Surgeors 6: 99. 1943.
Stcnbuck, J. B.: Two Cases of Successful Suture of Penetrating Stab Wounds of the Heart,
With Some Obscr\'ations on the Subject, J. Ml. Sinai Hosp. 7: 520, 1941.

Wood, P.: Electrocardiographic Changes of a T- Pattern in Pericardial Lesions and in Stab
Wounds of the Heart. I,ancct 2: 796, 1937.

Scott, R. \V., Fell, H., and Katz, L. N.: The Electrocardiogram in Pericardial EfTusion;
Clinical. Am. Heakt J. 5: 68, 1929.

Herrmann, G., and .Schwab, E. 11.: Some Experimental and Clinical Electrocardiographic
Observations on R-S-T and T Changes in Pericarditis. Tr. A. Am. Phvsicians 19: 229,
1934.

Noth, P. If.: The Electrocardiogram in Pericarditis, Thesis, University of Minnesota.
1938.

Noth, P. 11., and Barnes, A. R.: Electrocardiographic Changes .Associated with Pericarditis,
Arch. Int. Med. 6.1; 291. 1940.

I'orcro Sarabia. A.: EIcctrocardiografia en las heridas del corazon, Thesis, University cf
Chile. 1940.

Hoizmann, M.: EIcktrokardiographischc Befunde bci Perikarditis, Hcivct. med. acta
.3: 249. 19.56.

Blau, M. IL: Wounds of the Heart, Am. J. M. Sc. 210: 252, 1945.

Blumg.art. IL L., Schicsinger, M. J., and Zoll, P. M.: Angina Pectoris, Coronary Failure
and Acute Myocardial Infarction, J. A. M. A. 116: 91. 1941.

Steffens, W.t .Arbeit und Gesundhoit. Hcfl 27. Hcrzsteckschussc, Leipzig, 1936, Georg
Thicme.

ADDENDUM

Since this article was sohmitted for publication, four of the five patu-nts with persistently
almormal ekftrtx'ardiograms listed in Talde \'I (Cases 6, 8, 10, and 14) were re-e.\amined during
.\ngus£ through October. 1946. approximately two years following the examination recorded in
Table \'i.

Tlieir st.atus as far as the presence or absence of symptoms is concerned remains unchanged
except for the occtirrence of mild dyspnea upon o.xV'rf ion in Ca-e 8. Physical e.xamination revealed
nn notable change in CTrdiac findings and no pulsus paradoxicus or venous tiistention in any case.
Mol-rate hyp.Tt« rision apiXartnl in Case H>. Roentgenograms were practically identical in all
evse, « \r.'pt Case 10, in which there xx-as .an increase in the transverse diameter of the lieart of
'>5 The sliglitness of the change and the presence of some rotation of the thorax

neg.it, till- 'ignifiivance of this finding. The e!<‘ctr<x:nrdiograin in Case 6 show'ed disappearance
<4 low vultaee. ,a rh.mge in the T wave' in Lead I from isoelectric to tiiphasic, those in Lead \k
from diph'i'-ie to irna rted and persistence of T-tv.ave inve.-sion in Liaad'- \'. and W. Tiiesc changes
in rh, T w.ax.-s might have been <!ue to ,a change in the position of tiie heart from an intermediate
so a 'rsmyirtic.d jm-itfon. In Case 8 prolongdl auriculoventricul.ar conriuction persisted, but the
r y .nes h-. L. .i<h \\ .-itid were slighiiy Jess deeply inverted. The T w.ave-s in Lead Vj beoame
H ntirnidlv ufiright. In Ca'C lOthere was no significant change in the e-Iertrocartlio-

noth; ecg patterns in penetrating wounds of heart 753

gram. In Case 14 the T waves in Leads I, II, and Vs became low upright from diphasic and
those in Leads V 4 and Ve normally upright from low upright and diphasic, respectively.

In summ 3 r 3 % during this two-year period there was little change in the history-, ph^'sical, or
roentgenograph ic findings in these four patients. The electrocardiogram of one patient remained
unchanged, those of two showed minor changes, while that of the fourth patient revealed definite
improvement in the status of the mjmcardium. .

A CLINICAL EVALUATION OF POWDERED HUMAN BLOOD CELLS IN
THE TREATMENT OF ULCERS OF THE EXTREMITIES
ASSOCIATED WITH VASCULAR DISORDERS

Miltox W. Axdersox, M.D.,* Nelsox W. Barker, M.D.,t and
Thomas H. Seldox, M.D.J
Rochester, Mixx.

T he treatment of ulceration of an extremity which is affected by vascular
disease is frequently a serious problem. The ischemic ulcer associated vith
occlusive arterial disease is notorioush' indolent and resistant to local or topical
applications. It may have been produced by major or minor trauma or local
infection or it maj’ persist after the sloughing of gangrenous tissue. It may occur
at the site of amputation of a digit or portion of a limb. It is usually infected
and its base is frequently choked with leucocytes. Because of ischemia the
tissue at the base and margin of the ulcer is very sensitive to heat, cold, and chem-
ical irritation. Detergents or other topical applications which have e^'en the
slightest tendency' to cytotoxicity may affect such ulcers adversely. The use
of ointments or wet dressings is often tolerated poorly. The ulcers are frequently
painful. In spile of measures designed to produce vasodilatation and improve
arterial blood flow, they may persist for weeks or months and cause prolonged
suffering and dbability.

The so-called stasis ulcer associated with chronic venous insufficiency which
follows thrombophlebitis or complicates extensive primary varicose veins is
somewhat le.ss serious and may be easier to heal. However, it is often large,
indolent, and infected, particularly when neglected. Many such ulcers will
respond favorably to rest in bed with elevation of the limb and the application of
almost any bland wet dressing. Stasis ulcers, also, are sensitive to strong or
irritating solution.*;, ointments, or f>owders. Some are very resistant to any
type of treatment and even take skin grafts poorly.

The use of concentrated human blood cells both in the form of the natural
gelatinous mass and in the form of dried powder as a topical application arose
from the attempt to utilize this by-product of plasma extraction. There is con-
siderable evidence that healing processes arc promoted b}- blood cells. Nature
provides a crust of dottcM blood over lacerations and abrasions of the skin.
Under this crust granulation and cpithelization progress, fl'he crust undoubtedly
Ji-rves ns a protection from e.xogenous contamination and may be a nutritive
Kt!f)ply for the reparati\'e process. Dentists dread the occurrence of “drj’
following extractions, in which there is no clot to organize, contract,

for letb'.lotSon Ap.-ti 20. 1010
•VvT.dv \rt XtMsOfU', Xtftjro rotitidvlnn
f-r CHrlr.

,n pn Majo Ctirlr

ANDERSON ET AL. : POWDERED HUMAN BLOOD CELLS 755

and fill the defect. Seldon, Lundy, -and Essex^ actually observed accelerated
growth of vascular and connective tissue in the rabbit ear in the presence of an
old hemorrhage.

Naide^ reported promising results in eleven of fifteen cases in which he re-
moved blood from the patient’s antecubital vein and allowed it to clot in ah ulcer
crater. Moorhead and UngeU first used as a dressing for ulcers the gelatinous
mass of concentrated human blood cells from which the plasma had been ex-
tracted. They were impressed by the decrease of purulent secretion, stimulation
of healthy granulations, and the impervious covering which was created.

Difficulty was experienced in the handling of human blood cells in their wet
form in their early use at the Mayo Clinic. For that reason one of us (T. H. S.)
proposed the use of dried and powdered human blood cells. In an earlier report,
Seldon. and Young‘s outlined the method of preparation and technique of applica-
tion. As a result of these and subsequent observations, it was felt that the favor-
able effects of dried and powdered blood cells in the healing of wounds and ulcers
were due to some nutritive factor within the cells which is more or less specific
in its action.'*’®

Murray and Shaar" prepared a paste of red cells with tragacanth and hex>''l-
resorcinol. They observed more constant relief of pain with this mixture than
with the powdered form. In addition to the nutritive and protective property
hypothesized by other observers, they expressed the idea that the crust also
ser\^es as a mechanical scaffolding to support epithelization.

It is our purpose in this publication to attempt an evaluation of the efficacy
of powdered human blood cells in the treatment of chronic ulcers of patients ad-
mitted to the hospital service for peripheral vascular diseases. All of the patients
had definite vascular insufficiency as the basis for the ulcerations. The patients
were entirely unselected in that they included all those treated with blood cells
over a period \Vhen they came under the observation of one or all of us.

Needless to say, a controlled study comparing the results of various forms of
local treatment for vascular ulcers of huinan beings is an impossibility since
no two patients present lesions of identical size, duration, and character with
identical underlying vascular pathologic changes. Conclusions must, there-
fore, be based largely on the clinical impression of the physician who has seen and
treated similar patients. In many cases it was possible to compare the effect'
of powdered blood cells with that of other topical applications which had been
used previously during the period of hospital treatment for the same patient.

MATERIAL AND METHOD

The series to be presented here includes forty -six patients divided prirnarily
into two groups on the basis of the underlying vascular disease. In twenty-
nine patients arterial insufficiency was the primary vascular factor, and in the
remaining seventeen, venous insufficiency was the primary factor. A further
breakdown of the cases into specific vascular diseases gives the following dis-
tribution; thromboangiitis obliterans, sixteen; arteriosclerosis obliterans, thirteen;
post-thrombophlebitic venous insufficiency, ten; varicose veins with venous

rArii.r. 1. ThkomhoanViutis OuMTKkANs

756

AMERICAN' HEART JOHRNAE

ANDERSON EX AL.: POWX)ERED HUMAN BLOOD CELLS

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758

AMERICA-V HEART JOURNAL

necrotic

L foot nml Deep and Boric acid and peni- 30 Fair result; two small ulcers healed;

shin necrotic cillin dressings large ulcer 30 per cent healed

ANDERSON ET AL. : POWDERED HUMAN BLOOD CELLS

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760

AMERICAN HEART JOURNAL

nciolcnr, super- Attempted skin graft, 8 Poor result: generalized eczema

ficial boric acid dressings 5 veloped

T.xm.r, l\’. Pkimauv V\hk<>si-; Viuns Wnu Vi.sot’s Inm'i hcm.nxy

l-nrKC (6 by R shin Irregular Long saphenous liga- 27-L Good result; almost complete heal-

8) L ankle and deep tion, boric acid and 23-R ing

2 by 4 tyrothricin dressirgs

2 by 5 Rankle Infected and Various ointments. 6 Fair result; 50 per cent healed

dirtv boric acid dressirgs

ANDERSON ET AL. ; POWDERED HUMAN BLOOD CELLS 763

insufficiency, seven. , Diabetes mellitus complicated three and polycythemia
vera four of the cases of arteriosclerosis obliterans.

Cultures were obtained from only fifteen ulcers. Streptococcus hemolyticus
and Staphylococcus aureus grew in three cases (Cases 9, 10, and 44); Staph,
aureus alone from six ulcers (Cases 15, 21, 27, 28, 37, and 45); Str. hemolyt-
icus alone in one (Case 11); and Escherichia coli alone in one (Case 26). The :
other four cultures coi^tained, respectively, diphtheroids, micrococcus, pseu-
domonas, and combined Staph, aureus and Streptococcus viridans (Cases 14, 20, 21,
and 34).

On. admission to the hospital, nearly all of the patients exhibited a certain
degree of local cellulitis, active exudation, or gangrenous slough in or about the
ulcer. Initial therapy to clean up the ulcer and surrounding tissue consisted
usually of either soaks or dressings of warm saturated solution of boric acid or
0.5 per cent tyrothricin dressings. In a few cases potassium permanganate
soaks (1:10,000 dilution), irrigation with penicillin solution, or application of 5 ;
. per cent sulfathiazole ointment was used for this same purpose. Many patients
not included in this series showed good response to these measures, which were'
then continued, and local application of powdered blood cells was not used. For
this reason, the ulcers which were treated with powdered blood cells were those
which proved resistant to the usually accepted hospital regimen. .

All patients received treatment which was aimed to relieve the underlying
vascular disease. Those patients who had occlusive arterial disease’ were treated
with rest in bed, warm environmental temperatures, and the Sanders oscillating
bed. The use of tobacco was forbidden. Typhoid vaccine and lumbar sym-
pathectomy were auxiliary vasodilating procedures employed in several cases of .
thromboangiitis obliterans. Phlebotomy and phenylhydrazine therapy sup-
plemented local treatment in patients with complicating polycythemia vera.
Diabetes mellitus when present was treated with diet and insulin. When venous
insufficiency was the underlying factor, the involved extremities were kept ele-
vated. Orally administered sulfadiazine or parenterally administered penicillin
was used to treat spreading local infection whenever indicated.

Minor surgical procedures, such as removal of sequestra in underlying
osteomyelitis and removal of nails in subungual lesions, were performed to .
give better exposure of the ulcers for local therapy (Cases 3, 4, 7, and 24). Two
of the ulcers in patients with thromboangiitis obliterans were at the site of ^
guillotine amputation for gangrenous toes (Cases 11 and 16). Blood cells were
applied as adjuncts before and after skin grafting in two patients (Cases 38
. and 44).

The mode of application and the method for preparing the powdered human
blood cells were similar to those outlined in earlier reports from the Mayo Clinic.^
After the ulcer had been cleaned with wet dressings, the powdered blood cells
were applied with a sterile spatula or swab or dusted on from a container with
a shaker top. The entire surface of the ulcer was covered with the powder and
then loosely covered with a dry sterile dressing. Exudate absorbed from the
tissues caused the powder to form a hard crust resembling that seen commonly
on traumatic abrasions.' Sometimes seepage from the ulcer caused the cell

704

AMERICAN* HEART JOURNAL

criut to Stick to the dressing and this was genth' removed once daily. Any
remaining senim was gently sponged from the bed of the ulcer wth sterile sponges
and a new layer of blood cells was applied. E\'entually. as healing progressed,
a point woukl be reached where the crust no longer stuck to the dressing. Then it
v-as allowed to remain intact unless there was evidence of exudate underneath,
which pre\ented contact between the cells and the bed of the ulcer. In these
cases, tiio crust was loosened by soaking in boric acid, solution or b)^ apph'ing
flressings moistened with boric acid solution and was remo\*ed with a sterile for-
ceps, and more powdered blood cells were applied. When healing was complete,
the crust was either allowed to fall ofT spontaneously or was soaked until it softened
enough to be peeled off.

RESULTS

D.ila concerning the cases in which powdered blood cells were used and
results of this treatment are given in Tables I, II, III, and IV. In the final
o>lumn is listed the condition of the nicer at the time the patient was dismissed
fr«im the ho^pilal or at the time powdered blood cell therapy was discontinued.

I li;. 1 'C:v-K< !2'.- n, ThroniSoata-ilU^ «ltli Ff»r)pr<*iious «1c<t of bfd of riKlU toenail.

Th'’ uk'i? ((Ill b«':i priSf-n! tor two jo,-sr>: No ovidonc'* of Itraliitc not'^fi (luriitp local treatment
t>rotbricln. ntu-r intravcnotis aisn ij i^trtitioii of t>plu’J(! \acrtiir’, or after lun bar f-ympatliVtic
i-*v c'wrt-ctotnj. 6, S-snv u'cer aUi'o-t bcalta (lays oficr trratn'ftn with jKtwdt'rcd blood c<'ll«!

wa*. br-nia Titc wlc-r w.t. omiiJh'lOj l.falul on the nlnctt'cnih day of treatment.

The re-nlU’ in ihoM^ patientb v,iu. left the ho-pltal before complete healing occurred
and wh<» were given cells and itwtruciioiis in their use at home are li.stcd as per-
centage of ulcer luesletl ({ ;»><*?. 1, 11, lo, 21, 23, 27, and *10). (Complete healing
w,"!* [ifevenied in cA-ws by the prc.wnce (»f exposed bone or a persistent sinus
tiact ii) the base of the ulcer (Ca-e? 2, 18, 21. and 24), In two cases, powdered
b:*..4 cil!- were used preopiTasively and pi>i,top(‘rati\'eIy where large defects
Wer. o.%en4 with split -thickne-- skin grafts (Vast-, 38 and 44). Treatment

ANDERSON ET AL. : PO\TOERED HUMAN BLOOD CELLS

765

Fig, 2 (Case 16). — a. Thromboangiitis obliterans with ulcer at site of amputation of right first toe
for gangrene. The patient had previously undergone lumbar sympathetic ganglionectomy. The
ulcer was very painful and had failed to show any evidence of healing when treated with w'arm boric
acid soaks, boric acid dressings, and tyrothricin during a period of six weeks, b. Same ulcer after treat-
ment with powdered blood cells for tliirty-flve days. Pain was relieved and ulcer was 80 per cent
healed.

Pig. 3 (Case 11). — a. Thromboangiitis obliterans with deep gangrenous ulcer at site of amputation
of right first toe and removal of distal half of right first metatarsal. The ulcer had been present for
eight months. Tyrothricin wet dressings had been ineffective, b. Same ulcer almost completely healed
after treatment with powdered blood cells for twmnty-eight days.

m

l^r

.•< 11 .. 1 ** '(i

y-'fiii'., • -• ',V V ^ ;■ '- ‘i

F{if 4 (Cost' — <i ArtfrioscU^roKis obliterans with diabetes mellitus and iitfcctcd ulcer in largt
callus over plaiuar’stirfnce of fifth metatarsal head. The ulcer had been itreseni for two mouths.
h. Fame ulcer completely healed thirty-one days after treatment with powdered blood cells had been
begun.

■ V--

*T ■m- it t, *> ’ • •'i - ’* ■ •» » - j'

• £ ' '■ • ts rf.' .{i'tvi; - £' :<§-i ,.

>'■ i:ii "■>£. rritn-vry xnrlcoie vein with ehroi ie venous InsutTUdency and ulcer which had
sr than two year;?. No lieallOK' had follow ed licatinn and selero.«:is of long saphenou.s
i'ary varie#-., ?% Fame ulcer healed twenty-seven day.s after treatment with jifiwdt-red
! In'e;;, ntrlrd.

. ANDERSON ET AL.: POWDERED HUMAN BLOOD CELLS 767:

with powdered blood cells was discontinued in one case of stasis ulceration
because of poor results (Case 34). In this patient severe generalized dermatitis
developed. Powdered blood cells failed to control gangrenous ulceration in one-
patient with thromboangiitis obliterans in which guillotine amputation of a toe
was required. Subsequently, the site of amputation healed rapidly during treat-
ment with powdered blood cells (Case 4). Figs. 1 to 6, inclusive, show the
results of treatment.

On the basis of observation on the progress of healing, Table V summarizes
the results in the various types of vascular disease. In this table, good results

Fig. 6 (Case 32). —a, Clironic venous insufficiency caused by ancient iliofemoral thrombophlebitis
with large ulcer of one year’s duration at site of two previous ulcers. Attempted skin graft had failed '
one month before this picture was. taken, b. Same ulcer healed twenty-four days after treatment uith
powdered blood cells had been started.

Table V. Results of Treatment \^ ith Powdered Blood Cells

1

results

DISEASE

CASES

good

FAIR

POOR

Thromboangiitis obliterans

16

10

5

1

Arteriosclerosis obliterans

13

5

7

1

Post-thrombophlebitic venous insufficiency

;

6

3

1 1

Varicose veins with venous insufficiency

7

3

4

0

Totals

46

24

19

• 3

7fjg AMERICAN I1E*\RT JOURNAL

iiuUcate that the powdered blood cells appeared to be superior to other local appli-
cations. Fair results indicate that the ulcers healed but probably not more rapidh-
than might have been expected with other local applications. Poor results
indicate failure to heal or intolerance to treatment with powdered blood cells.

COMMENT

The use of jtowdercd human blood cells as a topical application for chronic
ulcers of the extremities associated with vascular disease is one of several methods
of bland and nonirritating local treatment available to the physician. In
order to evaluate its effect, tve have reviewed a series of cases in which the
patients were treated by this method at the iMayo Clinic. Despite the fact that
patients with tilcers associated with venous insufficiency are more frequently
.‘^cen on the hospital service than are those with ulcers associated with other types
of vascular disease, fewer of these received this form of treatment since they fre-
f|uent!y responded well to other bland local applications.

It is our impression that in approximately bne-half of the patients with both
the ischemic ulcers and stasis ulcers treated with the powdered blood cells, healing
v.’as much accelerated. This is based on previous experience with similar tilcers
in jiatients with comparable degrees of vascular disease in whom other methods
of local treatment were used and in those in whom a prolonged trial of other local
applications had been made without evidence of healing before the jjowdered
blood cells were used. In approximately one-half of the patients in whom pow-
dered blood ct'lls were used, it is questionable whether healing occurred any more
rapidly thatt it would have with <jther bland local applications. In a few patients
less healing occurred or the treatment was not well tolerated. Occasionally, it
was nec^es.stirv' to rdternate for peritids of a few day’s treatment with powdered
red h}o(j<I cells and treatment with bland wet dressings f)r lyroihricin solution.

It is difficult to determine whether the favorable re.sponse occurs from
TKirtia! desiccation, from some healing factor in the cells, from nutrition .supplied
by the crust, or merely because the crust is protective and entirely nonirritating.
Never? hele.-.s. it is encouraging to observe progress in the ulcers, with first a
puckering of tin* surrounding skin, then a freshening and reddening of the gray,
av;iM‘ular ba'=e. and finally granulations with epithelium creeping in from the
margin^. Certain disadvantages of wet dre.ssings. such as maceration of the
-nkin ami chilling, are avoided with this “dry” method of treatment.

Care is nece-sary in remoN'ing the crusts and in applying the new dressing
each tlay but, once the dre.^-ing has been applied, it need not bo touched for
twenty-four hout- or .‘-Jtmelimcs longer. This has the advantage of simplirilj-
and tequire.'- little tint**. Painful ulcers may become a little more painful during
the fir-i day the priwdcred blond cells are applied. /Xfter that, pain is ustially
fele ved. X.itmally, ifse use of blood cells in dealing with vascular ulcers is
"tspplemerunry to the iC'C of treatment to improve circulation and not a sub-

■'titfito |nr it.

ANDERSON ET AL. : PO^VDERED HUMAN BLOOD CELLS 769

REFERENCES

1. Seldon, T. H., Lundy, J. S., and Essex, H. E.: Effect of Certain General Anesthetic Agents

on the Small Blood Vessels in the Ear of the Rabbit, Anesthesiology 3: 146, 1942.

2. Naide, Meyer: Treatment of Leg Ulcers With Blood and Concentrated Plasma, Am. J. M.

Sc. 205; 489, 1943.

3. Moorhead, J. J., and Unger, L. J.: Human Red Cell Concentrate fcr Surgical Dressings,

Am. J. Surg. 59i 104, 1943.

4. Seldon, T. H., and Young, H. H.: Use of Dried Red Blood Cells in Wound Healing, Proc.

Staff Meet., Mayo Clin. 18: 385, 1943.

5. Seldon, T. H., Lundy, J. S., and Adams, R. C.: Powdered Erythrocytes for Dressing of

Wounds and Ulcers, S. Clin. North America 24: 814, 1944.

6. Seldon, T. H., Lundy, J. S., and Adams, R. C.: Stimulation of Wound Healing — New Use

for Powdered Red Blood Cells, Anesthesiology 5; 566, 1944.

7. Murray,. C. K., and Shaar, C. M.: Red Cell Paste in the Treatment of Ulcers and Chroni-

cally Infected Wounds, J.A.M. A. 125: 7,79, 1944. .

STUDIES ON THE VASCULARIZATION OF THE AORTA
I. The Vascularization of the Aorta in the Normal Dog

J. G, SCHLICIITER*

Chicago, III.

T he possibility exists that diseases of the aorta are related to disturbances
of the vascularization of its wall. This possibility was subjected to an e.x-
peritnenlal investigation in which (1) the vascularity of the aorta in several species
of animals and in man in health and disease was studied by injection with radio-
paque material and (2) the effects of e.xperimenlal interference with this vascu-
larization were analyzed.

In the present report the technique of studj’ing the vascularity of the aorta
is presented and the vascularization of the aorta in the normal dog is described.

TECHNIQUE

The hearts and aortas of fifty-seven dogs were obtained post mortem. The
aortic vasti vasorum were injected in one of two ways. In the first method a
glass cannula was inserted into the aorta, either at the arch or in the descending
portion, facing upstream and tied firmly in place. All tlie branches of the aorta
above the cannula except the coronara^ arteries were tied with catgut near their
origin from the aorta. In the second method, one or two of the coronary artery
firnnches, either of the riglit, of the left, or of both, were cannulated with the
cannula facing upstream. Before injecting the coronary branch or branches,
the coronary ostia in the sinus of Valsalva and the ascending aorta were occluded
by means of wet cotton to prevent leakage into the aorta.

The injectinit material used was the gelatine-lead carbonate-mercuric sul-
fide mixture described by Dock.* It was injected under a pressure of between
150 to 200 mm. Hg in the various experiments by means of the apparatus de-
v<dopefl by .Schle.singer.- Tiie aortas were opened and .x-rayed ; after the tissue
w.is prcjM-rly fixed, microscopic sections were prepared.! The x-ray technique
u.-(‘il was: 40 kv.; 30 Ma,; l]4 sec.; a fine focal spot; anode-film distance, 30
incln's; paper film holder and nonscreen film.}

RESULTS

Asccfidu;^ Aoritj . — This study revealed that the ascending aorta of the
tusrm.al clog is supplied (1) by vesecis arising from the left and right coronary

X**’’ nt-sKirimr-rit. XUcltart Rt-c'sn Hosidfat.

A. I> Na>.t Fun.! for Carillox-asculnr UcMivircli. Tills <|pii,'irtcn«it Is In

r-n m O.*’ Mirh-I*! nr.— iSf I'ounflntion.
f..* XUiy 4, 1‘UO.

•j*. . HP i f ■!.(. F'iUn'fatlon, '

‘tr * for itip rooppfaUrin of Uio PatlioloKy Uepartmeiit In prciwrlne

^’^* *^*^ tin- roopf-fation of tlu' x-ray J>cp;trtm'*nt In olitalnlnR tbo

SCHLiCHTER: VASCULARIZATION OF AORTA 771

arteries, (2) by vessels arising from the great vessels originating in the aortic
arch, namely, the subclavian, carotid, and innominate arteries, and (3) by vasa
arising directly from the lumen of the aorta. The vasa from these three sources
form a rich anastomotic network (Fig. 1,). Since the dye used is too coarse to
fill vessels less than 10/i in diameter, the anastomoses observed consist of vessels

to’’;’'’.

p Vt/s iv,j

Fig. 1. — Injection of the vasa of the ascending aorta demonstrating their origin from both coronary
arteries (below), from the vessels of the arch (above), and directly from the lumen of the aorta. In-
jection with cannula in the arch of aorta.

Fig. 2. — Injection of the first branches of the coronary arteries which supply the vasa of the
ascending aorta.

W.^. d

Fig. 3. — ^Anastomoses between the vasa arising from the right coronary artery and those arising
from the ieft coronary artery. The left coronary artery was occluded at its orifice and the right coronary
artery was injected by caimulation.

Fig. 4. — A preparation with an accessory ostium of the right coronary artery (the thick oblique
%'essel in the lower part of aorta). Note the predominance in the ascending aorta of the vasa arising
from this coronary artery.

772

AMERICAN HEART JOURNAL

lu'A'ing tliree coats. The entire description of the vasa given below will therefore
be confined to vessels of 10^ or more in diameter. Analysis soon revealed that
the network was made up of'(l) an adventitial network and (2) a medial network.
The former was found to be far more extensive than the latter.

Adventitial Netivork: This network is supplied by vessels from the coronary
arteries and from the large arteries of ‘the aortic arch.

The first branches of the coronary arteries are the vasa to the aorta and
pulmonary artery. These spread upward in the adventitia anteriorly and poste-
riorly over the ascending aorta. There are rich anastomoses between the branches
of the left and right coronary arteries; anteriorly they are located in the region
of the aortic-pulmonary groo^'e and over the pulmonary" artery; posteriorly
they are in the region of the aortic-auricular groove and on the posterior aspect
of the aorta (Figs. 1, 2, and 7). As a matter of fact, the anastomoses are so abund-
ant that the vasa of one coronary artery can be filled via the aortic branches of the
other coronary artery (Fig. 3).

When accessory ostia of cither the left or right coronary artery exist in the
sinus of \'alsalva, they are the chief origin of the aortic vasa (Fig. 4). It has
been staled that the ve.ssels of the dog’s aorta arise predominantly from the
right coronary artery in most animals.* However, our findings do not bear this
out. Usually no predominance was found in our series except in those instances
in which accessory ostia were present (Fig. 4). Actually we found :

Xo preponderance
Left prep<jndcrance
kislif preijondemncc
.Arco'.sory

•15 tings
2 dogs
.t clog.s

7 tings, in tthicli tlierc was a right
accessory’ o.stiiini and right
preponderance in 5 dogs, and
a left accessory ostium and
and left preponderance in 2
dogs

t r. - Irrftnehi-. cif t!ie left and rntht ct.rojiar> artery •.upjilylnK the root of (he sort.*! and

-,X' ‘■-•■’ti.n.e;’ ,• \iit5; ta,-, ,,r ojf,, ri.rieitis the direct from the lumen of Uio aorta In the upper

(••(••he- ‘5 5‘^‘CtrO^i *'? tte

ill- r. . St.-tc* ftt.rrs t!i<* of (!>•• aort.^ Itipction h> aortic camiut.a In the arch wIUi cor-

< -t-i 4 to.! ^-n H’, S},. Jr nrii'iiy’

-SCHLICHTER: VASCULARIZATION OF AORTA 773

- In addition to the vasa from the coronary arteries described, other vasa .
to the aorta arise more distalty. These are the arcuate branches which supply
the aorta and the aortic fat pad (Fig. 5). These arcuate branches anastomose
freely with the other aortic vasa.

The other source for the adventitial network of the ascending aorta arises
from the large arteries of the aortic arch and from the pericardium, descending

Fig; 7 , — Anastomoses in tho adventitia. Hematoxylin and cosin stain (X •'>0).

Fig. 8. — Ostium of a direct vessel from the lumen of the aorta fdled with dye. Hematoxylin and eosin

(X10).

774

AXfERICAX HEART JOURNAL

from the pcricardical reflexion. They anastomose extensively with the rasa
.'rising from the coronary arteries as well as from the branches of the bronchial
arteries which participate to a slight extent in the supply of the aortic wall
near the bifurcation of the pulmonary artery.

.f/ta/ffi/ Xelu'ork: The medial network is supplied by branches arising from
the adventitial network and by vessels arising from the lumen of the aorta. The
former ib the more abundent source of supply.

\’asa from the adventita can be traced as far as the inner third of the media
and anastomoses of these medial vessels can be seen in the outer and middle thirds
of the media. The vascular supply of the media is not as rich as that of the
adventitia (Fig. 7), and the extent of the anastomoses and the number of vasa
decroa-be progressively in the media as the intima is approached. Medial anas-
tomoses occur not only between branches arising from the adventitia but also
between these adventitial branche.^; and vessels arising directly' from the lumen
of the aorta.

t'J.; ^ - - Din ft % (M'-. t fmni Ui«' )nin''ri of tin- .nort.-t which om !>*• followed to the ndcldk- tlilnl of the media

Homatox.vUn and rosin stain ( XOT).

When the .ascending aorta is opened, small luinina arising in the intima can
1“' ;<vn grossly: in injected specimens, iJiey stand out as red points. The.'^e
c-in he followed .and their branching traced in the x-ray pictures and in
inirro-ia>p!c ‘'ecitons (Figs, 1 , 5, and S). The convincing demonstration that these
ve— arit-e and .tre supplied from the lum.-n of the aorta was made in those
f 'px rinv-rits in uhidt the dye vas injected via an aortic cannula in the ascending

Fig. 10. — Direct vessel from the lumen of the aorta anastomosing in the middle third of tho media
with a vessel arising from adventitial network. Intima above. Hematoxylin and eosiii stain (X56) ■

Fig. 11. — Stomas and small vessels below 10 m diameter arising directly from the lumen of aorta. Hemd-

toxylin and eosin stain (X204).

776

AMKKICA.V JrEART JOURNAL

.iorta facing upstream and in tvliich the orifices of the coronary arteries had been
conipietely occluded (Fig. 6).

Those vasa arising from the lumen of the aorta spread into the inner and
middle third of the media and even reach its outer third and can be seen to
anastomose with adventitial vessels (Figs. 9 and 10). On microscopic examina-
tion numerous small openings can be seen which are too small in diameter to be
injected by the dye (Fig. 11). The larger vessels, lO/j. or wider, arising directly
from the lumen of the aorta, could not be found in the ascending aorta in dogs
having acccssora' coronary* ostia; however, the smaller stomas, below lOp, were
still demonstrable.

Arch and Descending Aorta . — Vessels arising directly from the lumen of
the aorta and injectable by the dye used could be demonstrated also in the arch
and descending aorta. These vasa and those arising from the large arteries of
the aorta are the origin of the adventitial and medial plexuses of the arch and
descending aorta. The adt'cntitial plexus becomes progressively less extensive
as one progresses from the ascending to the descending aorta. On the contrary
the numinw of intimal vessels increases progressively along the downward course
of the aorta.

DISCUSSION

The present study has demonstrated that there is an extensive and elaborate
vascular supply to (he aorta, richest in the ascending aorta. Its origin is from
branches of the aorta, which give rise to an adventitial and a less extensive medial
plexus, and from intimal vessels, many of which are more than 10 n in diameter.
As the adventitial plexus becomes less and less enlensiv^e in going downstream,
the mmilKT of vessels arising from the intima increase, thus ensuring an adequate
blood supply to the aortic wall.

The prt'scnce of vas:i in the aortic wall had been demonstrated by Robertson.^
Di.ecrwt npening.s in the lumen of the aorui were previously noted by Woodruff’*
in two dogs. \\'inteniitz and co-workers^ injected small stoma.s in the lumen
of the aorta with India ink and found an intimal plexus by this metins. However,
it is not established that titis India ink injected plexu.s constitutes a capillary
Vascular plexus. It may represent a network of intercellular space.s into which
the highly ditTusihle India ink was forced by the injection method. When a
cfKirser injection mass is employed, as in the present study, no intimal plexus
can Iw demonstr.uetl. The only vessels, of 10 // or more, found in the intima were
miming from the lumen to the media. The nourishment of the intima
is thus depvndeni-upon diffusion from the lumen of the aorta, from the medial
v,s;-nilar ph-xus, and from the scattered intimal vasa. Whether or not this i.s
'’Uijplenunted by a capillary network within the intima must remain undecided.

schlichter; vascularization of aorta ' 777

, SUMMARY

1. The vascularity of the aorta in fifty-seven normal dogs was Studied by an
injection technique which disclosed the presence of vasa 10 ix or more in diameter.

. 2. An elaborate s^'-stem of vasa was found consisting of an extensive ad-

ventitial plexus and a less extensive medial one.

3. These plexuses are supplied by vessels arising from the coronary arteries
and the larger arteries originating from the arch of the aorta. In addition, vasa
;arising from the lumen of the aorta course through the intima to join the plexuses;
the number of these aortic intimal vasa increases progressively caudad.

I am greath- indebted to Dr. Louis N. Katz for his guidance and suggestions during the prog-
ress of this investigation.

REFERENCES

1. Dock, W.: J. Exper. Med. 74: 177, 1941.

<2. , Schlesinger, M. J.: Am. Heart J, 15: 528, 1938.

3. Robertson, H. F.: Arch. Path. 8: 881, 1929.

4. Woodruff, C. E.: Am. J. Path. 2: 567, 1926.

5. Winternitz, M. C., Thomas, R. M., and LeCompte, P. M.: The Etiology of Arteriosclerosis,

Springfield, 111., 1938, Charles C. Thomas.

Clinical Reports

RIGHT-SIDED AORTA WITH ATYPICAL COARCTATION INVOLVING
OSLY THE LEFT SUBCLAVIAN ARTERY. HYPERTENSION

C.M’TAix Arthur M. Master
Medical Corps, United St.\tes Naval Reserve

T he cate to be described concerned a young man, J. C. 0., 22 years of age,
Seaman, first class, in the Na\y. He had been healthy all his life and in-
deed athletically inclined. At college he had played tackle on the freshman and
varsity football teams. While attending a midshipman school in the Navy he
was examined for promotion but was found physically unfit for a commission as
ensign because of hypertension. On March 14, 1945, he was admitted to a U. S.
Naval Hospital to appear before a board of medical surv'^ey for observation and
report.

The young man was asymtomatic. Physical examination disclosed a person
of unusually fine physique, who was tall and weighed 175 pounds. There were
a few physical observations of note. Over the base of the heart a short sj^stolic
murmur was heard. The heart rate was slow, usually ranging from 45 to 60
beats per minute. The left radial pulse was definitely weaker than the right.
In fact the pulsations in the brachial, axillary, and carotid arteries of the left
upjj>er extremity were smaller thaji the corresponding arteries of the right side.
The bltJod pressure in the right arm was moderately but definitely elevated;
the readings were 158-170/60-76. The pressures in the left arm were normal,
104-124/70-80. The definite abnormalities were therefore the small left radial
pulse and the hypertension in the right arm.

The routine laboratory tests were not of significance. The Kahn was
negative. Kidney function was excelleni. An electrocardiogram disclosed a
sinus bardycardia, the rate being about 42 beats per minute (Fig. 1).

The hypertension in an upper extremity, particularly in a young man,
suggested the diagnosis of coarctation of the aorta. This diagnosis was dis-
missed. first, on clinical grounds and. second, by x-ray film of the chest. There
was no abnormal relationship of the blood pressure in the upper and lower ex-
tremities,’* no delay in rise or force of the femoral pulse, and no sign of collateral
ciraifation in the chest wall, anteriorly or posteriorly, on inspection or by palpa-
tion. Nor did an x-ray film (Fig. 2) give any evidence of erosion of the ribs by
dilated intercostal arteries serving as collateral circulation.

The blfKjd pressure in the lower extremities was not decreased but pre.^ented
ifje cu«^tom.'uy elevation above that obtained in the upper limbs. The right thigh
anc.ria! tension was 200' iOO and the left femoral blood pressure was 200/90.

Pulse iracing.s of the right radial artery compared with that of either of
tne femnr.'il .arteries confirmed the clinical impression that there was no retarda-

■n f oj.lnjsirs sna «.rt forth in this article arf tJ!o>!c of f ho writer and arc
rcCf^Urr iff of the Xsvy Department,

f, r pnt '(eaUon Nor J J roj.'-.

noi lo r»e con«ia4'r<HJ

•Electrocardiogram shows no abnormality. A sinus bradycardia is present: rate, about 45

beats per minute.

■Teleroentgenogram reveals a normal globular-shaped heart. The aorta and aortic knob arc

on right side instead of on left.

AMERICAN HEART JOURNAL

7^u

\<.n <»f the pulses in the lower extremities. In typical coarctation of the aorta.
(.libCTved an a\-erage delay of 0.03 second in the pulse of the femoral

aruTV.

'Fhe same teleroentgenogram of the chest which aided in disposing of the
(liagnci-i^. of coarctation of the aorta disclosed a right-sided aorta (Figs. 2 and 3).
Thf di.ignobis of this congenital lesion was confirmed by fluoroscopy. The inges-
tion of the barium mixture revealed the esophagus, at the level of the aortic arch,
be displaced anteriorly and to the left of the aorta instead of being behind this
'-tnuTure (Fig. 3).

ric a - l>uti'ral view film illsclosc.; l.arium-niloa t«:oplmKUS anterior to tho arch of tho .lort.n. Normall.\

the esophacu.5 Is behjtid the aorta.

.‘Mthoiigh the diagnosis of right-sided aorta was definite, this still did not
e.Kplain the diminished left radial pulse (Fig. 4) nor the hypertension in the right
arm. To explain the small pul.>e in the left forearm a search was made for a
left cervitMl rib. None was present in X-ray films of the chest. Nor was there
atiy variation in tiie course <jf the left radial artery. The left upper extremity
was completely normal in all other respects. The color and t<’mperature were
goiKl. The grip of the left hand was just a,s powerful as that of the right.

We tsow considered two congenital anomalies of the left subclavian which
o>uld expl.ain the decrea<ied pul.'-e of the left arm. A left subclavian artery
h.t*- been known to originate on the right side in right-sided aorta and to be com-
pre-,.-t'd in its ){.ng jjath to the left thora.x.’ Also a localized coarctation of the
b ft ^ubckivian artery, such a? was recently described by Grishman, Sussman, and
SteinlPTg,^ would he a® plausible an explanation. These investigators used the
artgior.udi'ntraphic technique %vhich they have advanced so successfully. WV

deesd'-d that rlirKirast injection would elucidate the problem. Several

master: right-sided aorta with atypical coarctation 781

Rig. 4. — Phonocardlogram taken at the apex and pulse tracings of both radial arteries. The left pulse
is distinctly smaller than the right and more gradual in its rise.

Fig! .S.~ Angiocardiogram demonstrates a right ventricular filling with the diodrast substance
passing valves of pulmonary artery. The septuih is more convex than usual, probably indicating a
hypertension in the left ventricle. (The ca-vdty of this chamber appears to be increased in size.)

~$l AMERICAN HEART JOURNAL

angiocardio 4 raphic studies were made.* In the first (Fig. 5), the diodrast is
in the rigid ventricle and puhnonar}' arter\'. The latter is of normal size and its
^•aK•cs arc visible. The cavity of the left ventricle which is not filled with diodrast
appears to be increased in size and the ventricular septum appears to be more
c-Mtve.x than usual, both of these findings being the result of the hypertension in
the aorta.

Fig. 6 is an illustration of the opaque solution in the right ventricle, pul-
monary' artery, and the right and left branches of this wssel.

rtc r. - AtipjontnlenTn!’' thi- <Jlc«!rsst PTitorlnK Oio Ji-rt and rlslit pulmonary arteries.

The final diodrast film tFig 7 ) shows the substance in the left ventricle and
clearly in the aorta and in the right innominate and the left carotid arteries.
There i« no sign of the left subclavian artery. This latter \’essel wn.s atresic.
The small left radial pulse was thus accounted for by a narrowed left subclavian
artery, Tlie aorta itself was normal in size and "measured 2.6 cm. in the sup-
ra.^tnus region, 2.5 cm. at the arch and about 2.1 cm. in the descending portion.”
There was no sign of hypoplasia or narrowing of the aorta sucli as Grisbman
and Co-workers* di'^covered in their patients.

TIu' final abnormality to be explained was the hypertension in the right arm.
I hi-' w.ts definite and had been present for some time. This conclusion was
‘•upp''n«l. first, by the e.\'amii5ation of the fundus which disclosed slight indenta-
tj!”} .tf ihe vcitss by the arterie- where iltey cro.ssed, and second, by the slightly

'O'h ti r $ i'«h r'f ttf '-ai-.iran. tL<' n.i'vtKi-r.rlorht ct the MeuM IIo<«pUol,

V« ^5. N Y . O ^ s;i«n5rsi!<i.-r-.pl If xtiplit". «prp iratltr tit tli.i! ln<itltutlon {riM 5, (5 niid 7) nnU

master ; right-sided aorta with atypical coarctation 783

enlarged left ventricle and, the displaced interventricular septum which had been
forced to the right (Fig. 5).

The hypertension could be present in this patient as a coincidence, just as
it is found not infrequently in so man 3 '- other young men in the Armed Forces.
A more plausible explanation is that the hypertension was associated with the
coarctation of the left subclavian arterjc In the three cases of localized coarcta-
tion of the left subclavian, described by Grishman and co-workers,^ a hyperten-
sion in the right brachial arterj'- was found in two patients.

Pig. 7. — Angiocardiogram sliows the diodrast in the aorta. AVliite shadows are present where the ,
right, innominate and left common carotid arteries normally arise, but there is no evidence of a left
subclavian artery.

COMMENT

Unequal- radial pulses have been noted in coarctation of the aorta.^*^.
King'^; Table IV cited nine case reports gathered from the literature in which the
blood pressure in the right arm was definitely higher than that in the left. These
patients may have possessed a coarctation of the left subclavian artery, but the
aorta proper was narrowed since the blood pressure of the legs was lower than that
of the arms. This is the discrepancy in blood pressure of the upper and lower
extremities found in the ordinary case of coarctation of the aorta.

Grishman and associates^ were the first to make a diagnosis of the atypical
coarctation of the aorta with absence of left radial pulse by means of the diodrast
method. Gur case differs from theirs in that our patient revealed no extensive
involvement of the aorta at the level of the isthmus and distal to the arch;
the left radial pulse was not absent but was diminished in our patient; and,
finally, a right-sided aorta was present.

AMERICAN HEART JOURNAL

7S4

Grislinian and co-workers suggested that the diagnosis of atypical coarcta-
tion of the aorta may be suspected on clinical and polygraphic examinations but
can be proved only by angiocardiographic study. We think that one siiould
go further. We predict that a small or absent left radial pulse, with a hyper-
tension in the right arm, but with the normal expected arterial tension in the
femoral vessels, will often disclose a localized coarctation of the left subclavian
artery. On the basis of the report by Grishman and co-workers, we suspected
this diagnosis in our patient before the diodrast solution was used for confirmation.

When the left radial pulse is small or obliterated, other common conditions
should fir-st be thought of and eliminated before the diagnosis of coarctation of the
left subclavian artery is hazarded. A large cervical rib is not uncommon. Many
normal people can shrug their shoulders back and up and temporaril}' decrease,
or totally obliterate, the radial pulse. Of course, in our patient the pulsation was
})ermanently affected. A congenital anatomic variation in the course of the
radial arteiy, an aortic aneur\’sm, or a tumor compressing the subclavian artery
is to be considered before a diagnosis of coarctation of the left subclavian artery
is made.

Hypertension is almost invariably present in typical coarctation of the
aorta.*** Steele^ believes that not only is a systolic hypertension of the upper
extremities pre.«ent, but he maintains that the diastolic arterial ten.sion in the
lower extremities (and '‘infercntially the peripheral resistance”) is often in-
creased. He is of the opinion, therefore, that the hypertension in the typical
coarctation of the aorta is a compensating mechanism to increase the general
vascular tone in the whole body, lower extremities as well as upper. In our
patient, then, the hypertension would simply be associated, perhaps refle.xly,
with the localized atresia of the left subclavian artery. It would be a systemic
response of the arterioles to constriction of a large branch of the aorta.

The nerves in the carotid sinus and the arch of the aorta play an important
role in controlling blood pre.ssure. In a congenital malformation involving the
n<irta at the mouth of the subclavian, it is not illogical to expect an efl'ect on
arterial tension in the body, and seemingly this is always an elevation. The
decrx'ase in tension in the left arm was due to mechanical constriction of the left
.‘lubclat.'tan arterj*.

The bradycardia (heart rale, 42 beats per minute) may have been the slow
puke so often met with in athletes or it may have been produced by the nerve
mechanism in the aorta in a way similar to that by which the hypertension was
produced.

The absence of .sympioins in this patient with both a right-sided aorta and a
rtjnrrtafir.n of the left subclavian artery is not surprising. The former congenital
mnlformatitui is often discovered by accident. Lewis- studied the typical type
of cixirctaiion of the aorta in English Army veterans of \^’o^ld W'ar I. He fountl
that nmtiv had pi-rformetl hard phy.scal work for many years witii no symptoms.
In co.-irri.iiion limiteil to the left subclavian artery, the arm undoubtedly receives
a ‘•ijfttcitnt blsKid supply from collateral sources.

ISIA'jTER : RIGHT-SIDED AORTA WITH ATYPICAL COARCTATION 785

, _ ' , , SUMMARY

A case has been described of right-sided aorta with coarctation of the left
subclavian artery. The diagnosis was made clinically and by ordinary x-ray
film and then confirmed by angiocardiographic films.

A small or absent "left radial pulse in the presence of a hj^pertension in the
right arm and a normal expected blood pressure in the lower extremities should
lead to the consideration of the diagnosis of a localized coarctation of the left
subclavian artery. Such causes as cer\dcal rib, anomalous course of the left
radial artery, tumors, and aortic aneurysm must first be investigated.

With a localized coarctation of the left subclavian artery, just as with the
typical coarctation of the aorta, a hypertension is usually present. It is probably
a reflex mechanism originating from the nerves in the aortic arch and producing
an increased vascular tone in all the extremities.

Localized coarctation of the left subclavian artery frequently is discovered by
accident. The patient presents no anatomic or physiologic defect in the left
upper extremity except the small or absent left radial pulse. Hard work is quite
compatible with the lesion.

REFERENCES

1. Abbott, Maude E.: Coarctation of the Aorta of the Adult Type. A Statistical Study and

Historical Retrospect of 200 Recorded Cases, With Autopsy of Stenosis or Oblitera-
tion of the Descending Arch in Subjects Above the Age of Two Years, Am. Heart J.
3: 381, 574, 1928.

2. Lewis, T.: Material Relating to Coarctation of the Aorta of the Adult Type, Heart 16:

205, 1933.

3. Grishman, A., Sussman, M. L., and Steinberg, M. F.: Atypical Coarctation of the Aorta,

With Absence of the Left Radial Pulse, Am. Heart J. 27: 217, 1944.

4. King, J. F.: The Blood Pressure in Stenosis at the Isthmus (Coarctation) of the Aorta;

Case Reports, Ann. Int. Med. 10: 1802, 1937.

5. Steele, J. M.: Evidence for General Distribution of Peripheral Resistance in Coarctation

of the Aorta. Report of Three Cases, J. Clin. Investigation 20: 473, 1941.

PAiX OF UNUSUAL DURATION DUE TO PROGRESSIVE CORONARY
OCCLUSION WITH ASSOCIATED .MEDIASTINAL TUMOR

Maurice A. Doxov.a.n, iM.D.

Schenectady, N. Y.

A ngina pectoris due to n\yocardial ischemia has been thoroughly studied
by Keefer and Resnilcd They reviewed the former theories regarding this
symptom complex and concluded that the coronaiA^ circulation became inadequate
to meet various demands of the heart muscle when increased above its basal
level Lately. I ha\-e attended a patient who had steady, continuous, severe
chest pain for eight days. He was unable to sit or lie down during this period.
In cither position, pain of an agonizing, tearing nature developed. Even while
he was standing, some pain ^^'as present, but this was controlled somewhat
by forty to si.xty 1/100 gr. nitnjglycerine tablets in the twenty-four hour period.
The problem was complicated further by an unexplained tumor mass in the
mediastinum between the posterior surface of the heart and the dorsal spine.
This case i.s reported in detail because of the problem in diagnosis, the unusual
fact that the patient was compelled by his pain to remain in the standing posi-
tion continuously for eight days, and finally because of the finding at autopsy.

CASE REPORT

T)ic patient was a 45-year*oW man, whose weicht was 2l)'J pounds, height 5 feel 11,1^ inches;
5se luad nlwats heeii well up to twenty-two months prior to this illness. Previously the patient
h.ii! been aide to walk -evernl miles with ease and had*enjoye<i hunting and fishing trips. The
f.uuib bistort was neg.ni\e: his father is alive and well at the ago of 72; two older brothers have
no history of he.iri dise.ise; and his mother diet! of .1 cerebral accident at the age of 52.

I he present illnc's began one year an<i ten months prior to death. At that lime the patient

v. a^ f'mphned at heavy labor, lifting considerable weight during an eight-Itour day. Graelually
he noted the onsi i of -ubs^trnal distie-s when lifting. During the course of the ne.\t few weeks
a sense of pres-ure wa* present in the chest after a walk of three blocks at an average rate. He
had a complete plpsir.il examination at this time, including gastrointestinal x-rays and an electro-
cauiiaar.im. All studii s w ere negat i\ e except the electrocardiogram, w hich show ed low voltage T

w. Tii's tbrteagl'.out with .a definite cove T in the fourth Uad (Fig. 1, ,1). He w.as advised that some
m\«h' irdi."*! damage was present, presumably on the b.isis of coronary -clrrosis, given nitroglycerine
for .icute attacks of piin, and advi.sed to keep his activities within the limits of the myocardial
rfo rve. He g.aw up he.ivv work and secureii emidoyinent of a light, setientary nature, How-

pvn on walking continued, but this w-.is prompt Iv relieved by either rest or nitroglycerine.
Hef*mtitnj.s<5 jn this vtate until r.arly January, 1945. at which time he wms rcferrid to me for further
studv.

Tile is'ttu.il tindings nt this time were a dear-rut liistory of angina on efTort, an entirely
e- t pii’.s-f.iil «-\.imin,ition ixcepi for a bloorl pressure reading of 174/110, a neg.ative Wasscr-
mane, .^nd an cs‘« uSnliv norma! eli-ctrocardiogram (Fig. 1, B). A comparison of this tracing tvith
D - f i.A'sn f‘jrfm.rly (Fie. 5. .!) -hows improvt'd voltage in the QRS comjilexes and all T waves,
i u< rr are nune" pte'',iu, sncniding more pronouncerl shirring of QRSj and some RS-T

Tfam ef r.arctloViiri'. rilS» Hosjiital

{[•-.--’Jria f..- f.-iUfc-.tJnn J.-sfi g'., JPSC

7>«e

DONOVAN : PROGRESSIVE CORONARY OCCLUSION 787

segment changes in Lead IV F, but it was felt that minor deviations of this sort in a single tracing
did, not justify a definite diagnosis.^ A repeated tracing (Fig. 1, C) was made immediately aft^
the patient had exercised b 3 ’’ the two-step method of Master.* This suggested temporary myo-
cardial ischemia since it showed a depression of more than 0.5 mm. in the RS-T segment in Lead I
and Lead IV F. The blood pressure and pulse rate had returned to their original levels within
two minutes. After the last tracing was studied, the previous opinion of coronarj' artery’- disease
was confirmed, similar advice offered, and enteric-coated aminoph\diine, 3 gr. four times a day
was ordered. The patient returned to his attending ph\'sician and was not seen again until five
months later, thirtj" hours prior to death.

Fig. 1. — Electrocardiograms suggesting myocardial changes.

.At this time the history obtained was that for the preceding week the patient had been unable
to remain in any but a standing position. Liberal injections of morphine and atropine and papa-
verine.by mouth as well as injection were of little help in controlling the pain. The only procedure
of value was to allow the patient to stand upright and take from forty to sixty 1/100 gr. tablets
of nitroglycerine during a twenty-four hour period. Although previous studies suggested that
coronary insufficiency was present, it appeared questionable that this was the entire problem.
Accordingly, the patient was hospitalized. Complete fluoroscopic and x-ray studies of the heart
mediastinum, lungs, esophagus, and great vessels were"made. Two of these roentgenograms are

789

DONOVAN: PROGRESSIVE CORONARY OCCLUSION

reproduced (Fig. 2). The report and conclusions of the roentgenologist* were as follows: Ex-
amination of the chest showed a symmetrical bony cage. The cardiac shadow generally was within
the limits of normal in size, but there was a tumor mass projecting from the posterior surface of
the heart, deflecting the esophagus posteriorly and to the right and producing a large central
. filling defect with no particular obstruction. The mass might have originated in the wall of the
esophagus, but was' not associated with the mucous lining. Impression: Mediastinal tumor or
cardiac aneurvsm.

Fig. 3. — Photograph showing tumor mass in Fig. 4. — Photograph showing esophagus opened and

the esophagus. split tumor mass in situ.

At the conclusion of the first and only possible scries of x-rays, a careful esophagoscopj' was
considered for the following day. Meantime the patient secured enough relief from Demerol,
100 mg. intramuscularly every three hours, coupled with occasional injections of morphine 14 . gr.,
to permit him to sit in a chair for-several hours and to obtain some degree of relaxation. There
were no changes in the general physical examination except that the formerly elevated blood
pressure was no\v 122,/100. At no time during the illness was any dige.'^t've disturbance present.
Unfortunately, due to technical difficulties, it was impossible to secure an electrocardiogram at
this time. The patient was much more comfortable until ten minutes- prior to death. He

*r>r. K. L. Mitton.

790

AMERICAN HEART JOURNAL

.i^.iLuted -ndcknK and stood up, crxing out with unendurable chest distress. The nurse left
to ec‘ nr.otht.r hjpodtimic, but when she returned the patient had fallen to the floor and was

dt.ad

E\<i!)!iKalton. — .\utopb\ was performed twelve hours aftex death.* The es-
'entnl gro". fmdines reported were as follows: (I) Peritoneal cavity: The diaphragmatic domes
were in th( tlnrd and fourth innerspace on the right and left sides, respectively. The high posi-
t-on of the domes was apparentK caused bv the greatlv enlarged liver. The serosal surfaces were

If *1 l'’ht'iinniieri)rrjspli of laree coronarj nrterj sliowine ori;ani?< d. ciilciHt <1 tliminlnih

— di and s],.n‘. (2) 1 itt p, rirardtal c,i\5t\. eont.aineti about 59 r.c. of straw-colored

ti-'uj I1>i ht trt wi .ehtsi 49 ) gntni' 1 he t ptcanlial fat wa-- increased. 'I'lie cavitic - were not
dflstf! fti! -honfl no h-on- The right \tntricular wall was 4 nun. thick and flabby.

( o,. h tt n'ficahr w.iH w t-. i\ rn-uracti d an<l had a tiiaint tc r of 1.8 centimeters. Small foci

' **' inti rvtntnrul.tr -<ptum Poth coronar% arteries were tortuous
't irifaflsfeldt rsr! !. PrUl otofM

DONOVAN: PROGRESSIVE CORONARY OCCLUSION

791

and rigid. On cross section the walls were calcified and the lumen of the left descending coronary
artery was of pin-point size 3 cm. from its origin. The right coronarj' was also calcified and tKe
lumen was entirely obliterated 2 cm. from its origin. The smaller branches of the coronary
arteries were patent. The ascending aorta, the arch, and the descending aorta showed a few
elevated plaques in the intima but no calcification. (3) Mediastinum: A firm, ov'^al tumor mass
(Figs. 3 and 4) was palpated in the posterior mediastinum. On dissection it was found to arise
in the wall of the esophagus. The tumor was well circumscribed 6 by 4.5 by 4 cm. and located

Fig. 6. — Photomicrograph (X 240) of the esophageal tumor shoi^ ing leiomyoma of the esophagus.

5 cm. above the cardia. The lumen of the esophagus above the tumor showed no distention and
there were no gross changes in the mucosa. The cut surface of the tumor was composed of gratdsh-
white trabeculated tissue closely resembling. leiomyoma. (4) Liver: The organ was markedly
enlarged and’ weighed 2,709 grams. The le't lobe extended to the left midclavicular line. The
capsule was smooth. On section, the cut surface was brownish red, smooth, and resilient. The
gall bladder and the bile ducts appeared normal. (5) .Anatomical diagnoses: coronary .sclerosis
with complete occlusion of the right coronary artery and partial occlusion of the left descending
artery; tumor of the esophagus; enlargement of the liver.

A^^I•R!CA^• HEART JOURNAL

7<U

i hi, t microscopic fnuHnsis reported were as follows: (1) Heart: Patcliy areas were

M.n in vhuh the nni'cle fibers were replaced by fibrous tissue. The nuclei in the muscle cell
A'lncent to the^e areas were enlarfrcd and square. .\ large coronary vessel (Fig. 5) showed e\-
ti n-r,e ('.alcihcation of the internal intimal layer and proliferation of the external intimal layer to
■uch a decr»-e that the lumen of the vessel was entirely obliterated. The adventitia showed no
ceiiular infiltration. The changes in the aorta were minimal. There was some splitting of the
mus! ie tiln-rs and fat droplets were found in the cells. (2) Esophagus; Sections taken through
1 he tumor (Fig. 6) showed the '.tratified squamous epithelium, the submucosa, and the nonstriated
nvode layer to be normal. (3) Microscopic diagnoses: leiomyoma of the esophagus; fibrosis
of myoc.ir*!imn; chronic passive congestion of liver.

DISCUSSIO.N

The main point of the presentation meriting further discussion was the un-
expected finding of a benign tumor of the esophagus associated with clinical
cortinarx' insufiiciency. There was nothing in the history or physical e.xamination
to indicate any esophageal disease. The x-ray studies suggested a further possi-
bility that a cardiac aneurysm rather than an esophageal tumor might be present.
Altlnnigh severe chest pain is seen frequently with myocardial infarction, its
continuous presence for an eight-day period is most unusual. Occasionally,
angina of rest or angina decubitis occurs, but even in these cases there are periods
in which pain is absent or when active treatment will terminate this pain for a
considerable period of time. It was the unusual presenting complaint of the
terminal illness coupled with the une.xpected finding of a mediastinal tumor that
occasioned some doubt regarding the otherwise clear-cut diagnosis of progressive
wrt m a r y i n su 1‘fi cic n cy .

In a recent publication by Harper and Tisceno,'* a review of the cases of benign
ttunor of the esophagus that have appeared in the radiologic literature was noted.
They list ffuiricen, to which they add two cases of their own. Among the
clinical symptoms .summarized by them, one in particular may have some
im}K)riance in conjunction with the case described here; namely, “Intermittent
retrosternal sensation of dull pain or of i)ressure or of an ‘aching sen.sation’
which were usually referred to the lower or middle part of the sternum, being
sometimes aggravated by lying on the back." Whether the tumor present in this
case was a factor wfiich prevented the patient from cither sitting or lying down
is open only to speculation. It has been found'' tliat the general blood flow is
greater in the recumbent position and thus the heart has more work to do than
with the patient sitting or standing upright. It is pos.'^ible in this instance
that the mycranlial reserse was so e.xhausted that standing ma}' have been
more etvntomical from the standpoint of heart efficiency. Vins/m,'^ in his mono-
graph on The Diagnosis and Treatment of Diseases of the Esophagus, states;
“.\Hhnugh benign tunior.s are not observed often, they occur frequently enough
to lequire consideration in patients who present unusual syniptfuns referable to
?h'‘ e.'-opluigu.''. Myoma, which Is the most common benign tumor of the esoph-
agttv, df not produce symptoms unless it attains considerable size. Diagnosis
ran rart-ly he tnadr* during life, but at many po.st-mortcm e.vaminations tumors
jat- typ^* are noted." In a cuiiMtleraiion of the diagnfr.ds of this condition he

DONOVAN : PROGRESSnrE CORONARY OCCLUSION 793

further states: “Roentgenoscopic study frequently reveals defects in the lumen
of the esophagus, which may suggest the presence of a large tumor that does
not cause obstruction to passage of a radio-opaque meal into the stomach.
When such defects are noted, benign tumor should be suspected. In many
cases diagnosis cannot be made without removal and microscopic study of the
tumor during life or at post-mortem examination.”

Thus it may be concluded that tumors of this type are not common and often
cause no symptoms nor signs during the life of the patient. On the basis of
these facts it is most likely that the clinical picture presented was due entirely
to myocardial ischemia resulting from progressive coronar}^ artery disease.

SUMMARY

This case is presented because of the unusual duration of chest pain, the
fact that the patient had to stand upright for a continuous eight-day period,
the extreme degree of coronary sclerosis with only suggestive electrocardiographic
changes, as well as the difficult}^ added to the diagnostic problem by the presence
of a mediastinal tumor of uncertain etiology. This is offered as a clear instance
in which the importance of the history, when carefully taken and properly
interpreted, is the deciding factor in the diagnosis of angina pectoris.

It is a pleasure to acknowledge the courtesy shown by Dr. Ellis Kellert, Ellis Hospital, in
preparing pictures and photomicrographs of the tumor, as well as the kindness of Dr. H. Dunham
Hunt, Saratoga Springs, N. Y., in furnishing the electrocardiogram reproduced in Fig. 1, A.

REFERENCES

1. Keefer, C. S., and Resnik, W. H,: Agina Pectoris; A Syndrome Caused by Anoxemia of the

Myocardium, Arch. Int. Med. 41: 769, 1928.

2. Graybiel, A., McFarland, R. A., Gates, D. C., and Webster, F. A.: Analysis of the Electro-

cardiograms Obtained From 1,000 Young Healthy Aviators, Am. Heart J. 27: 524, 1944.

3. Master, A. M., in collaboration with Nuzie, H. C., Brown, R. C., and Parker, R. C. Jr.:

The Electrocardiogram and the “Two Step” Exercise. A Test of Cardiac Function
and Coronary Insufficiency, Am. J. M. Sc. 207: 435, 1944.

4. Harper,. R. A. K., and Tisceno, E.: Benign Tumor of the Oesophagus and Its Differential

Diagnosis, Brit. J. Radiol. 18: 99, 1945.

5. Wffiite, P. D.: Heart Disease, ed. 2, New York, 1937, The Macmillin Co., p. 594.

6. Vinson, P. P.; The Diagnosis and Treatment of Diseases of the Esophagus, Springfield,

1940, Charles C. Thomas, pp. 153, 155-157.

COMPLETE AURICULOVENTRICULAR BLOCK AND BUNDLE
BRANCH BLOCK WITH INTERCURRENT
AURICULAR FLUTTER

Report of a Case

Jose Proenca Pinto de Moura, M.D.

Campinas. Brazie

T he association of auricular flutter with complete A-V heart block was
first demonstrated with electrocardiographic proof by Jolly and Ritchie
in IhlO’ and is very uncommon. DiGregorio and Crawford- found only two in-
stances in a series of 20,000 electrocardiograms. Willius^ reported only one
instance among 40,000 electrocardiograms. Up to 1939, only thirty-one cases
had been reported in the literature and since then, additional reports have not
increased the total beyond forty cases.

.'\mong the reported cases of auricular flutter with complete A-V heart
block, syphilis has been considered the most common etiologic factor, with
rlieumatic fever ne.Kt in frequency; liM^erthyroidism and congenital anomalies
have been thought responsible for a small number of cases. Coronao' sclerosis,
however, should also receive etiologic consideration since a large proportion of the
p-ilienls were over 50 years of age. Jourdonais and MosenthaP have suggested
n division of the cases into two types: (1) Patients who have both disturbances
consistently and (2) patients who have one arrhythmia consistently and the other
as a transient occurrence due to drug administration. Since it is frequently
impossible to determine whether or not drug action is concerned, this classifica-
tion seems rather unnecessary.

CASE REPORT

F. S.. a 25-ycar-oki man, was ndmittod to the CardioloKiotl Sena’ce of the Irmaos Pcnteaclo
on March 11, 1943, because of dt-spne.! on effort and at rest and edema of the f.ice, ab-
dojticn, .-md b'K';, The«e symptoms had developed .suddenly following ingestion of a vermifuge
in j.muary. 1943. From the first appe.irance of thesymptoms, heart failure progressed gradually
but .‘■teadsly. H\cept for long-standing colitis, the patient hati considered himself in good health
prior to his pre<ient il!t)e«-;. Hi* past medical history included epistaxis and “rheumnti.sm"
lapjiareniJy rheumatic fever) in childhootl, lie had several episode.s of dysentery and frequent
upper r. spiratory infections including pneumonia in 1941, at which date the sputum wa.s negative
for .id l-f.isi bariili. He had ii^ed alcohol motleralcly and had been active in sports, especially
footb-ill. 'rise birnify history was irrelevant.

Fhv^ica! ex.tmin.ition on ,idmis-ion to the hospital rcveali-tj a man of tall, slender build who
pslr- and orthopneic. The face, abdomen, and lower extremities were very edematous. The
fon il*. Wire hypertrophic- The teeth were carious. The thyroid gland was bilaterall}’ enlarged.
Hs! fv tile- at both lung base-. The heart was gre.'itly enlarged. The rhythm w.as irregular

t fw lie Dfrertc, nn do CoraQiio Or Pinto de Moura,

l!(«v£\^d for p!iMl«*at!on f*c'. in, )Oir,

Tin

DE MOURA : . AURICULp VENTRICULAR AND BUITOLE BRANCH BLOCK 795

Pig, 1 . — Electrocardiogram taken March 12, 1943, following admission to the hospital. Complete A-V
heart block and right bundle branch block with ventricular extrasystoles.

Fig.. 2.— Electrocardiogram taken Aug. 4, 1944. Complete A-V heart block persists but auricular
flutter has developed. The dominant ventricular complexes are now those which previously repre-
sented ventricular extrasystoles. '

7‘H} AMERICAN HEART JOURNAL

FIk. 3.™ ER'Ctro(v»r(llogratn takwi Aug. 5, 1914, following aUministralion of dipitnlis. Cornplolo
A-V In.-art block and auricular flutter are present ns on tlic precetllnp day (FJg. 2), but tlio dontlnant
vciitriculrir complexes are again tlioso which wore Initially recordwl (I'lg. 1).

i'L-, 4 . .. i:i.^;.„rar.HrHrrArtv n <;-pt, 27. H<t4. Complete- A-V heart block and auricular flutter p.x-
JUI rise h.-3!s have reverteil to the type which were lull bally exIraMstoles,

: DE moura; auriculo ventricular and bundle branch block 797

with a rate of 48 per minute. The heart sounds were diminished and a loud systolic murmur was
audible over the entire precordium. ArteriaT pressure was 120/50. The liver was enlarged.

■ Routine laboratory studies showed a negative blood Wassermann reaction. The blood
count Avas normal. Urinalysis w'as negatme except for slight albuminuria. A phonocardiogram
recorded a systolic murmur. An x-ray film of -the chest revealed a greatly enlarged cardiac sil-
houette. The electrocardiogram (Fig. 1) showed complete A-V heart block Avith right bundle
branch block and frequent ventricular extrasystoles.

The diagnosis Avas heart disease: (A) rheumatic fever, pneumonia (?); (B) cardiac enlarge-
ment, mitral insufficiency; (C) complete A-V heart block, right bundle branch block, ventricular
extrasystoles, congestive heart failure; (D) Class IV.

' The patient AA'as confined to bed and treatment included the administration of Salyrgan and
of Deriphyllin in 50 per cent glucose solution intravenously. Improvement folloAved and the
patient Avas soon able to be out of bed. From time to time he left the hospital AAuthout permission
and attempted to AA'ork but Avas soon forced to return because of aggravation of his symptoms.

In August, 1944, folloAving such an absence, an electrocardiogram Avas made AAffiich shoAved auricular
flutter (Fig. 2). It is noteAA'orthy that the complexes AAffiich had previously represented the pre-,
mature beats noAV constituted the dominant beats. Digitalis Avas then administered, folloAA'ing
Avhich the electrocardiogram (Fig. 3) shoAA'ed a reversion of the A'^entricular complexes to the type
Avhich had been dominant prior to the onset of auricular flutter. The next electrocardiogram, ,
made in September, 1944, shoAved that once again the beats Avhich originally had been ectopic
had become the dominant type (Fig. 4). No change AA-as present in the last electrocardiogram
made in November, 1944.

In December, 1944, heart failure recurred in severe form and progressed in spite of further
treatment AV’ith digitalis and salyrgan. Death occurred suddenly. There Avas no opportunity /
for terminal obserA'ations.

DISCUSSION

As previously mentioned, the association of complete A-V heart block
Avith auricular flutter is extremely rare. The present case is presented because
of the exceptional association of four defects: complete A-V heart block, bundle
branch block, coupled extrasystoles, and auricular flutter. It appears that the
rheumatic process affected the conduction system, cicatrization of Avhich produced
first the A-V heart block and then the bundle branch block. The extrasystoles
could be explained by the necessity for a pacemaker in the loAver center. Drug
action was not responsible for these phenomena for quinidine was Avithheld :
because of the possibility of producing embolism and digitalis Avas given only in ,
relatively small dosage. Because of the extent of the organic myocardial dam-
age, treatment could be expected to bring about little more than subjective im-
provement. Such actually Avas the case and the progress of the disease continued
almost uninterruptedly to its fatal termination.

summary

A case of complete A-V heart block associated with bundle branch block,
ventricular extrasystoles, and auricular flutter is reported. This combination '
of defects is very rare. The apparent etiologic factor AA^as rheumatic fever,
Avhich caused an unusual degree of damage to the conduction system. The
patient Avas observed over a period of seventeen months; he died of sudden acute
heart failure.

AMERlCiW’ HEART JOURNAL

TOR

I'hf author v.-i«hfs> to ovprt-ss hiV appreciation to his assistant, Mrs. Ruth Szysrka, for her
v.t’tiaMe a‘''i'-t.'inc<-.

REFERENCES

t. Joliy. .V. A., and Ritchie, W. T.; Auricular Flutter and Fibrillaticr, Heart 2; 177, 1910.

2. PiGrcjtorio, N. J., and Crawford, J. H.: .Auricular Flutter and Complete Heart Block,
Am. Hi-art j. 17; 114, 1959.

5 Willius, F. A.: .Auricular Flutter With Established Complete Heart Blcck, Am. He.art J.
2; 449, 1927.

t Jtnirdonais. L. F.. and Mosenthal, H. O.; Complete Auriculovcntrirular Blcck ard Auri-
cular Flutter With Obsenations of the Effect of Quinidire Sulfate, Am. Hr.\rt J.
11; 735. 1937.

Abstracts and Reviews

Selected Abstracts

Stein, L., and Wertheimer, E.; Cardiac Metabolism and Rigor in Thyroidectomized
Rats. Arch, internat. de pharmacodyn. et de therap. 71:129 (Nov.), 1945.

The fact that cardiac rigor develops more slowly in thyroidectomized than in normal rats
prompted an investigation of some of the conditions upon which the course of the cardiac rigor
curve depends. The studies were made on rats which had been fed a standard carbohydrate diet.
The hearts were removed from the living animals in sixty to ninety seconds, suspended in a Ringer
bath, and attached to a kymograph for recording their movement.

It was found that the heart produces a normal rigor curve only when it is isolated while the
anirhal is under deep narcosis. A shock tj^se of rigor curve, brief in duration, occurs when the
heart is removed after the rats are rendered unconscious by a blow on the head. Previous treat-
ment with caffeine or strychnine, as well as acute asphyxia or poisoning with KCN, produces a
similar result. Fatigue and exhaustion or thyrotoxic influence cause a marked curtailment of the
rigor curve. Digitals or cardiazol almost completely nullifies the effect of brain shock, asphyxia,

' or exhaustion on the rigor curve but do not nullify the influence of the thyrotoxic principle.

The cardiac rigor curve of thyroidectomized rats is essentially different from that of normal
rats. It is of greater duration and is not influenced bj’^ brain shock, caffeine, strychnine, exhaus-
tion, or digitalis. Acute asphyxia has less influence than it has on the curve of normal rats. Chem-
ical rigor produced by niono-iodoacetate poisoning is essentially the same in thyroidectomized
rats as in normal rats. The duration of rhythmic contraction of the thyroidectomized rat heart
in Ringer solution is' twice that of the normal rat heart. - Laplace.

Heymans, C., Casier, H., and Delaunois, A. L.; The Influence of .Alcoholemia on the
Proprioceptive Refle.ves for the Regulation of Arterial Pressure. Arch, internat. de
pharmacodyn. et de therap. 71:103 (Nov.), 1945.

Intoxication by eth)'! or methyl alcohol depresses the central nervous system and favors
the occurrence of a state of shock, especially post-traumatic cardiovascular collapse. A further
study of the subject was made to determine the effect of alcohol on the aortic and carotid sinus
reflexes because these are the mechanisms which regulate and maintain the normal arterial pres-
sure, and their suppression predisposes to cardiovascular collapse.

The experiments were performed on dogs which had been anesthetized with chloralosane and
were given artificial respiration. In order to limit the proprioceptive regulation of blood pressure
to the carotid sinus reflexes, the cervical vagus-aortic nerv'es were sectioned. The capacity of the.
animal to react against circulatory^ collapse was determined by occluding the two common carotid
arteries. When the normal compensatory reactions had been determined, a 25 per cent solution
of alcohol in isotonic serum was administered intravenously and the intensity of the vaso-hyper-
tensive reflexes of the carotid sinus was recorded at regular inten^als.

The results obtained indicate that: (1) weak doses of ethyl alcohol are capable, in the first
phase, of stimulating the vaso-hypertensive reflexes of the proprioceptive arterial pressure regulat-
ing mechanism; (2) the proprioceptive reflexes of the carotid sinus may suddenly become com-
pletely suppressed when the blood alcohol concentration reaches 0.2 to 0.4 per cent (this depressant
action predisposes to cardiovascular collapse) ; (3) the reflexes concerned in the automatic regulation

799 .

AMERICAN HEART JOURNAL

I,: .srUT!-*! p 70 "iirt.' art rapidly restored in proportion to the decline of blood alcohol lev'ol;
; isifovK a! ion with methyl alcohol produces a similar but more prolonged effect.

Lapl.ace.

Movin, H., OhUen, A. S., and Pedersen, .V. INI.: Arterial Hypertension — Nephrectomy.

.\rt.i inc^i. Scandinav. 119:439 (VI), 1944.

\ 6 vtar-o!d lioy with a history of hematuria and p> uria since the age of IS months and of
UK rt.i'-inclv severe headache.s for two years was found to have a blood pressure of 170/120. There
«a- no function of hi-= right kidney; the left kidney was apparently normal. The eye grounds
and the electrfKrardiogram were normal.

An attempt at right pyelography was followed in six hours by a severe hypertensive encc-
plialopathy. with three hours of convulsions and coma. Two other enccphalopathic episodes
nrrurred spontaneously during the ensuing three weeks.

The systolic blooii prc.ssurc fell to below 100 one hour after riglit nephrectomy was performed.
After thirty-six hours of severe oliguria with the blood urea nitrogen rising to 100 mg. per 100 ml.
the hoy recovered completely. He wa.s followed for eighteen months, during which period no
abnonnalitie.' of blood pressure or renal function were detectable.

The riglit kidney was the scat of severe chronic pyelonephritis with marked thickening of the
rap.sule and atrophy of the renal parenchyma. Microscopically the arterioles were greatly nar-
rowed and showed marked thickening of tlieir intimal and medial coats but no necrosis.

Tile author.s believe their c;iso demonstrates that excellent results may be expected from
nei>hrcclomy when iiyfx.Tlension, caused by unilateral renal disease, has not yet resulted in
significant damage to the opposite kidney or to the cardiovascular system. S.\YI5N.

Duanrie, VI.: On tlic “Parmloxic" .Action of the Syjnpathctic and the A’agns on the

Ooronarj Arteries. Ztsclir. f. Krcislaufforsch. 31:99 (No. 3), 1942.

The author cites and lielieves he ha.s <-onf)rmed previous reports in the literature that the
media of the coronary arteries contains a much larger proportion of spiral fiher.s than other artcrie.s.
'I’he action of spiral TiIkts is to •'horten thc vcs.sel and thus enlarge the lumen, producing effects
opp'site to that of circular fibers. Likewise, relaxation of spiral filx'rs results in lengthening of the
vr-ssel ami in a smaller lumen. .\ similar situation is said to ovist in the bronchial tree of human
iKant;, fZt'-chr. f. Kreisiaufforsch, 31:21 (No. 1), 1942). Human coronary arteries have, in addi-
tion. a wcli-develo[H:d longitudinal muscle layer which has an action similar to that of the spiral
fil-er-s It is propo-eti that in all ve.--cls the contraction of arterial and arteriolar muscle coats
ft -nits from symjwthetic stimul.ition but that the effect of such contraction is opposite in the
rf>rori.irics, since the lumen is enlarged through shortening of the vessel length. The results of
p>rasvmpithic stimulation arc opposite. Thus the postulation of a different muscle reaction in
toronary vc'-xU (am! the human bronchial tree) from tliat resulting in other arteries in the or-
V.jnisnt would Ik- unneec'S.iry. .Swfv

llorttiiigtoii. IL W., Ilsnit. 11. !)., Unit, II. II., Griffiths, G. G., Montgomery, If., Solley,
n. r., niul la-ahe, A\'. II.: Slinlirs in Khciimntic ITwer; II. Absorption of Salies--
fntes. .-Ann. Int. Med. 21:1029 (June). 191(j.

Ihi-. ft]Kirt ile.ils with oh-erv-ations made among a group of patients with rheumniic: fever
n: uhoni treatment consistt-d of lirge drise< of salicylates administered b> the oral, rectal, anti
sn:ra\( ;;s routes Hie lotnp-'irisons wen- madt- }»etween the atlmini.st?ation of sodium .salirylatc
;snd i.- .t'ct’. I Tins meriinition was given with and without soifiiim bicarlxmate. Otj

xh' O'- 'rfum *a!)r\{,irr levels it was conehidt-rl that salieylate is readily absr)rlx'd from tht-

op'- 1 t-n.I l!i> y.sstr.antvstsna! tract Imt K poorly ahsorlx-d from tlic' lower end. Tor this reason
.ofd.o'- rv t th.e. - .-iHi-yhte shotifd never In,- given in enteric-co.iied t.dilctsor by rectum.

5 tf •> --K v-s: l! tie- g.s« trir irrit.atson resulting from the admini-tr.ation of the ordin.ary tab-
4g --af-r'.l.te h'.- rtevith <an Ik’ miniuii.'ctl by flu* siutultaneous administration of

: : V SELECTED ABSTRACTS 801

food or bicarbonate. In their experience, bicarbonate sufficient for this purpose (60 gr. daily)
should not cause a definite reduction in the serum salicylate level. They also found that the ,

..i concomitant administration of bicarbonate did not reduce the blood level of salicylate below -
what would ordinarily occur without the bicarbonate. They also stressed the fact that there is .
practically no need for resorting to intravenous salicylate administration inasmuch as adequate
■ blood levels can be achieved bj^ giving the drug by mouth. Wendkos.

Fagiu, I. G,. and Schvab, E. If.: Spontaneous Mediaslinal Emphysema. Ann. Int.
Med. 24:1052 (June), 1946.

In this article the authors describe three new cases of mediastinal emphysema and review
all previously published cases. The differentiation of this condition from true cardiac disease,
such, as acute myocardial infarction, acute pericarditis, dissecting aortic aneurysm, and pulmonary ,
embolism is stressed. In this regard, the absence of significant electrocardiographic changes ‘
as a diagnostic feature of mediastinal emphysema is emphasized. The proper use of the roent-
■ genogram as a diagnostic aid is demonstrated. The frequent association of pneumothorax is also -
pointed out and its mechanism is briefly discussed. The benign and self-limited nature of spon-
, taneous mediastinal emphysema is reaffirmed. There is an adequate discussion of mediastinal
crepitation (Hamman’s signi as a diagnostic feature. Included are reproductions of sound .
tracings which show how the acoustic qualities of mediastinal crepitation differ from those of a
pericardial friction rub. Wendkos.

IVIoherg, G.: Intravascular and Extravasciilar Pressure in Valsalva’s Experiment.
Acta radiol. 27; 392 (No. 3-4), 1946.

• '• ThevalidityofWestermark’s method of measuring pulmonary artery pressure by holding the'
breath against a measured pressure which diminishes the size of the pulmonic vascular shadows
is questioned. The author believes that this or any modification of the Valsalva e.xperiment •; ,
would have a selective effect on the pulmonary arterial circulation only if the chest were open "

. and the lung inflated b}' the intratracheal pressure. The Valsalva experiment is asserted to con-
vert the whole of the abdomen and thorax into a chamber in which there is a relatively uniform .

. increase of pressure which would act on the great vessels and the right ventricle equally with the
pulmonary capillaries except '"or the elastic recoil of the lungs. This results in the blood being,
forced from the trunk into the extremities, head, and neck. The diminution in size of vascular .
shadows would thus be due to a smaller amount of blood in vessels of widely varying size and
pressure and not to an effect on the pulmonary vascular bed alone and would therefore have no . .
significant relation to the pulmonary' arterial pressure.

' ' . , ' Sayen. , '

Laquime, J., and van ITeersr»-ynghels, J.; A New Classification of Congenital Cardiop-
athies. Acta med. Scandinav. 118; 244 (No. 1-3), 1944.

A classification is suggested based on the presence or absence and the type of vascular shunt ’ •
between the greater and lesser circulations in congenital heart disease. This would avoid the use -
of cyanosis as a criterion as was done by Abbott. The difficulties involved in eraluating the multi-
plicity of factdrs.affecting cyanosis are detailed. The authors suggest cases be grouped as follows;

1. Those with no vascular shunt.

2, Those with a shunt, which may be of two types: ' ,

(A) Arteriovenous shunts, evidenced by reduction in carbon dioxide tension in the pul-

monaiy' arterial blood which can be measured by rebreathing various mixtures of a gas and obtain-
. - ing equilibrium. This group would include interventricular and aortic septal defects, patent
, atrial septum, patent ductus arteriosus, and transposition with septal defect.

(B) Venoarteria;! shunts, determined by studying arterial unsaturation in the systemic

- circulation. This group would include the tetralogies of Fallot and Eisenmenger, cor biloculare, '
and other similar defects. ' ' ' , ,

'Sayen.

americax heart journal

nrtmittjrr, IK: Proteimirin of Effort iind Its Significnncc in the Diagnosis of Congcsli\e

Ih-ort l ailiire. Acta med. Senndinav. 121; 252 (No. 3), 1946.

IKc believes that the concept of ‘'phj-siologic" proteinuria up to 2.0 to 8.0 mg. per

cent, fucH 1 -. iu^cd on the work of Morner (1895), is incorrect. The usual clinical tests for album-
iruirii are rdntncK inaccurate and arc negative unless a proteinuria of at least 5.0 to 10.0 mg.
i-r cent i-- present. Using precipitation by salicylsulfonic acid and a set of dilute solutions of
prci'ipit.a'cd scrum as comparators, proteinurias of less than 1.0 mg. per cent can be measured.
Of .'0 ‘’nornii!" patients, none showed more than 1.0 mg. per cent of protein at rest; exercise
;fonv knee bends; did not increase this significantly. Twenty-five of thirty patients with acute
febrile di'-cascs had 1.4 to 7.1 mg. per cent of proteinuria, whereas only 40 per cent of the group
eboued .1 positive albumin test by routine methods. Patients with acute glomerulonephritis
nr acute pyelonephritis showed increased proteinuria after e.vcricse. Those with chronic renal
di*-e.i.se did not

Nineteen cardiac jwtients without failure showed no increase above the author’s strict normal
.st.uui.trds at rest or after exercise. Of thirteen patients with congestive failure, exercise produced
significant increases of protein above their normal resting figures in patients with mild signs of
rmige-fion Patients with more severe congestion had abnormal proteinuria at rest and a further
consid'-rablc increase after e.xercisc. This occurred with left-sided failure and not necessarily
only when venous pressure was elevated. There was no quantitative relationship between the
.amount of proteinuria and the severity of congestive failure. In the absence of acute renal or
febrile systemic tlisease, a resting proteinuria greater than 1.0 mg per cent and a poste.\ertional
proteinuria greater than 2.0 mg. per cent in cardiac patients is felt to be evidence of congestiv'e
heart failure.

SaveN..

Solierf* 1).. and Sclilnehmim. INI.: The Effect of •Methyl.vnnthines on the Prothrombin

Time and the Coagulation of the liloud. Am. J. M. Sc. 212; 83 (July). 1946.

The investigations reported show that there is a definite shortening of the prothrombin
imu’ and of the plasma coagul.ation time following an intravenous injection of amiriopliyllinc. The
changes were often found within one hour after the injection, reached a maximum four to five
hours Iciter, and often persisted after twentv-four hours. Since the intravenous injection of theo-
phylline with sodium acetate had a similar effect, the action is not bound to the elhylenediamine
which i** ustfl as a solvent for the theophylline. The oral administration of mcthyl.xant hires was
likewise found to shorten the prothrombin and plasma co.agulation times. The possibility is
suggest cd that the iucrc.ascd coagulability of the blood may augment the danger of venous throm-
boM'i in the bedridden patient or the risk of coronary thrombosis in a patient with coronarx'
sclero'^is.

On the other hand, it is suggested that the inothylxanthincs may be of value as styptic agents
in hemorrhagic disease. Tlic cause of the hyperprothrombinemia jirotluccd by these drugs is
unknown, but a functional stimulation of the hepatic ti.sstic has been suggestetlasa causative factor.

Dukaxt.

Dc Tjiknts. C„ I’ovvlcr. E. F., .Jordan. P.. and Kisley, T. C. : Synipatlu'ctomy in Pori-
pliernl \'ns<Milar Sclerosi*!. J. A. M. A. 131: 495 (June S), 1946.

.nuthom di^cucs their c.xpcricnrcs in using sympathectomy for the treatment of peri-
phrnd. v.ic.-iihr s-rlcrosiH of the lower extrcmitic.s. The indications for .synipathecfomy were as
It; patients v, iiij popHie.al. fctnor.al. or aorticocrlusions nhoshowed a favorable response to
paravertebral hhv-k v.-ith. procaine .anti who=e vi'^ccml va.sctilar invajlvemcnt was subclinic.al or
inn hca.'.p'cg!,), no coronary occlusion, no .adv.anced nciihrosrlerosisl; patients with or vvith-
I at iLaliC'r-- vh'i <• chief nmiidiini w.is coniitniotts intractable I'urningpain .associnterl with ostco-
rl-.r, f.hrsitirs! relief from paravertebral block and who otherwise wouhi require a siipnt-
ci" nvlrr .tmput.atrm 'a cait^dgic snvtc?. Tbe .age grrnip laetween 40 and 50 was found to be most

SELECTED ABSTRACTS 803 -

; : The material consisted of twenty-five patients ranging in age from 39 to 66 years who were
placed in the. vascular sclerotic category because of (1) definite evidence of sclerosis elsewhere; -
.(2) absence of a history of segmental phlebitis or arteritis in earlier years and no involvement of
radial arteries; (3) high pulse pressure, hypertension, hypercholesteremia, or hyperglycemia.

The following results were obtained. Group I included nine middle-aged sclerotic patients
. with a previous walking ability limited to a few blocks. These patients were greatly benefited
• by lumbar sympathectomy; their walking ability improved, occasionally for unlimited distances;,
in two patients it improved to a point where they developed angina of effort. Group II was made., '
up of patients whose walking ability ranged from one-half to two blocks. Operation was under- ,
/: taken mainly to prevent gangrene. Not a single patient developed gangrene on the sympathec- .

■ tomized side; Uvo patients lost their legs on the side not operated upon, which were originally the .

better legs. Group III included patients requiring amputation or who had already lost one leg
. by amputation. As a result of lumbar sympathectomy the authors were enabled to do three toe ...
amputations and three louver leg amputations in the presence of a type of circulation which their ,
previous experience indicated would have necessitated a supracondylar amputation'. The patients,
in Group IV had intractable pain, diffuse osteoporosis, and glossy edema. These patients were ,
regarded by the author as belonging to the casualgic state. These patients also showed improve-
ment after sj''mpathectomy. Bellet ^

. , Lee\’y, C. M., Slrazza, J. A., Jaffin, A. E.: Fluids in Heart Failure. J.A.M.A. 131:

1120 (Aug. 3), 1946.

One hundred twenty-two patients with congestive heart failure were studied to evaluate the .
relative merits of restriction of fluid intake, allowing fluids ad libitum, and forcing fluids.

Currently, most clinicians allow only 1,000 to 1,500 c.c. of fluids daily as an integral part of'
their cardiac regimen in treating congestive heart failure. They feel that more may increase the ;
burden on the heart. Members of the ad libitum school feel that limiting or forcing fluids may.
may prove difficult, hazardous, or uncomfortable, whereas champions of the forcing-fluids school
of thought believe that with the ever-present renal function impairment in cardiac decompensation, .
more water than normal is necessary to eliminate normal waste products without having the kidney
work at maximum capacity.

All patients admitted to the general medical service with congestive heart failure were
, diyided into three groups; Group I consisted of th’rty-six patients on a restricted fluid regimen
of 1,200 c.c. daily; Group II was composed of forty-eight patients placed on a fluids ad libitum '
.regimen; Group III included thirty-eight pat ents who received a minimum daily fluid intake of . .
3,000 cubic centimeters. All patients were placed upon the same fundamental cardiac regimen, the
only essential difference being the amount of fluid intake. Patients were given an acid ash;
salt poor diet which provided sufficient calories, proteins, minerals, and vitamins, and at the same
time insured a low sodium intake, low salt intake, and an acid ash.

The following results were noted; In the group permitted to drink fluids ad libitum, the
average cardiac patient consumed approximately 1,700 c.c. of water daily in the summer and only
1,300 c.c. in the winter. Patients allowed to drink water as they desired w'cre much more com-
fortable than members of the other groups. In no instance was increased intake associated with
evidences of the circulation becoming overburdened, increase of decompensation, or water in-
toxication.

< Of the thiity-eight patients on a forced-fluid regimen with a minimum daily intake of 3,000 c.c.,

.■ seven (18.3 per cent) became nauseated and were compelled to discontinue the treatment. Of
those adhering to forced fluids, twenty-seven felt greatly improved. The average amount of fluid
, consumed daily by the individuals of this group was 5,750 cubic centimeters. In no instance did
pulmonary edema or hypertensive encephalopathy incident to cerebral edema follow the regimen
. of forced fluids.

' -Of thirty-six patients in whom fluids were restricted, 27.7 per cent complained of thirst , '
,(52.6,per cent of those observed during summer and 47.4 per cent during winter);. 13.6 per cent of :
-patients discontinued restriction because of thirst. Restricted fluids may lead to dehydration, ’

; with disorientation. . . > .

AMERICAN IIRART JOURNAL

«fs4

Tin -e nuthori; ronchide that with reMrictcd sodium intake, restriction of water is unccessaiA-
i*^s t jc.uinc rarrii-ir decom 5 -vensation---tl»at restriction of fluids increases the discomfort of the patient
and may prove deleterious. In most decompensated cardiac patients, forcing fluids will neither
retard nor facilitate compcntcitinn. The average patient with congestive heart failure should
he aHowci! to drink nvuer as it is dcsirctl and should consume enough to maintain a daily minimum
tirir.rsr.v outi)ut. \Mien congestive heart failure is complicated by sepsis, fluids should be forced to
fibrain nptiniiim therapeutic results. Likewise, water intake should be increased to ]wevent
istdivdraiinn where there is intrinsically intpaired renal function or excessive skin or urinary water
loss.

Bkixet.

Levy. H. I... White. IL 1)., .Stroud. W. I)., ami llillinan. C. C. : Overweight: Its Prog-

iiostle Signilleane.e in Relation to llyperlen.sion and Cardiovascular Renal Disease.

J. A M A. i:Ut 051 (July 20), 1946.

A statistical analysis was made of the medical records of 22,741 officers in the United States
Army trj determine the prognostic significance of overweight noted in the course of annual physical
examinations.

.■\n officer was considered to be overweight when he was heavier, by twenty pounds (nine
ki!ogr.ims( or more, than the standard given in army regulations, calculated according to height
and age. By .sustained hypertension was meant a reading of over 150 systolic or 90 diastolic
per.sisting throughout one examination and not followed in subsequent examinations by lower
kwels.

When the combination of ovcrwei.ght , transient hypertension, and transient tachjeardia was,
present, the probability of the later development of sustained hypertension was twelve times as
gre. 1 t as in normal controls. In the case of retirement with cardiovascular renal diseases, the
prolxalulity was four times as great. Overweight alone did not increase significantly the death
rate from cardiovascular renal diseases. Transient hyperten.^ion or transient tachycardia
or overweight by itself Increases the probability of the later development of susiaincil hyper-
tension and of cardiov-nscular renal disease.

Bicixkt.

Inmlolo. and Uc RysUy. C.; Clinical Studies on Venous Pressure. 1. Techniipie:

Venous Pressure in .V«»rmnl Imlividiinls. Cuore e Circ. 29: 97. 1945.

The autlmrs studied the venous prv.ssiire of normal subjects by the direct method. A v.aria-
tion from usu.d technique was the graphic recording of the venous pressure. Oscillations of the
venoi!*; p.w^'-ure due to three {Kisrible causes were observed: (a) arterial pulsations (transmitted);
(b' respiratory changes: (c) changes of the venous tonus.

The vennu'. pre,s<ure tracings varied in different individuals and at times presented ample
;:ml fn'qiK ut oscil! stions, caused by variations of venous tonus. Values between 20 and 1 70 mm.
wafer were ermsidered nornnl by the authors.

Li'is.ana.

Mnllen. At. S., and Pallares, D. S.;

r.ifdjf!!. Mexico 16: 22, 1946.

\ Study of Chronic Cor Puljm»nale. Arch. Inst.

*,{

I'o'.iriee'! eaw^of chronic cor pulmonale were studied from Imth a clinical and elect rocardio-
.i:ul|i-nn'. The nmiri symptoms and signs were paroxysmal rlyspnca, effort dyspnea,
cx.mo'.ix, jjrt** vt-nouK engt^rgement. Congestive fiailure was. revcalcrl by hepatic enlargement,
rd-m,’, taeaveardi t. .in<! prolongation of the arrn-to-tonguc time. .Accentuation of the hilar
f.,i i.l.-v,. .I ir> .i)} enbrgenient of the pulmon.'iry arterv was ol^scrved in over 90

ti'-r o !it of ilu' patif-ntx.

; , , . SELECTED Abstracts • 805 -

The electrocardiographic changes were : P 3 higher than Pi ; P w;ave inverted in Vi but upright
in Vp-. absence of Qi; presence of Si and Qy, small R wave in Vj, Vi, V 5 , Vo; deep S wave in V 4 and
Vo; T inverted, flat or diphasic in Leads II, III, Vp, Vi, Vz, and. Ve.

The above changes were attributed to dilatation and hypertrophy of the right auricle and
ventricle.

Luisada.

Elkin- D. C., and Banner, E. A.: Arteriovenous Aneurysm Follooving Surgical Opera-
tions. J. A. M. A. 131: 1117 (Aug. 3), 1946.

This case was reported because of its rarity. The authors have not encountered a similar
instance in the literature. Most of the cases of arteriovenous fistula which have been presented ;
in the literature have arisen as a result of war wounds or from injuries incurred in civilian life. ,
in this report, the authors described a case in which this lesion was produced during a surgical . '
operation, hysterectom\^ The most likely explanation of this occurrence is that in transfixing
and ligating blood vessels the needle used for this purpose injured the artery and vein at the same, . . ,
..time, with the subsequent production of a communication between them.

Following the removal of the arteriovenous fistula, the patient made an uneventful recovery.

Bellet.

Dock, W.: The Predilection of Atherosclerosis for the Coronary Arteries- J. A. M. A. .
ik: 875 Quly 13), 1946. ’ •

In this article, Dock makes two points; (1) that arteriosclerotic changes frequently occur . .
earlier in the coronary^ vessels than in other vessels and ( 2 ) that coronary artery' disease is more
■frequent in men than in women, especially before the seventh decade.

From a study of hundreds of soldiers who died of coronary disease, it was apparent that ..
cases of coronary disease without tibial, cerebral, or aortic lesions, which are exceptional after the' ,'
sixth decade, are the rule in men under 40 y^ears. Coronary’ thrombosis is not only much more,
frequent, but also often occurs as a result of a purely local atheromatosis. In those hearts ex-'
amined at necropsy it was noted that while most of the vessels were relatively free of atheroma,
many’ of them had unusually thick intimal layers at places in the coronaries where no lipoid had , • '
y’et been deposited and where there was no inflammatory reaction.

Although Spalteholz, Gross, and others mention the remarkable thickness of the coronary
intima, as compared with that of the radial, tibial, cerebral, or visceral arteries, this observation '
has been ignored by’ most pathologists and clinicians. No satisfactory’ explanation of the increased
, susceptibility of the coronary’ arteries to atheroma has been thus far advanced.

Dock was unable to explain the higher incidence of coronary’ disease in men as compared with > , T!
women from the level of the blood cholesterol or the height of the arterial pressure. In the
examination of hearts of y’oung adults killed in accidents, Dock observ’ed a striking difference in the
thickness of the coronary arteries in the two sexes. The men had thicker intimas: coronary’. -
, arteries of boy's no more than 18 years of age often had atheromas in them. In addition, sections; ^
were made of the right coronary artery, the left circumflex branch, and left descending branch of
• . twelve infants of each sex who died less than twenty'-four hours after birth. He observed in these

specimens that the thickness of the coronary’ intima in male-infants was about three times that in ■ '
female infants. ' . . ;

He believes, therefore, that the sex differences in coronary disease and, to some extent, the •
familial differences in incidence seem to rest on an anatomic basis. , . ,

Bellet.

Hinton, J- W., and Lord, .Tr.. J. W- : .Analysis of Surgical Failures and Fatalities FoIIom -
ing Thoracolumbar Sympathectomy for Essential Hypertension, N, Y. State TL
- - Med. 46; 1714- (Aug.), 1946. - ' ■ . .

, Although thoracolumbar sy'mpathectomy’ has a definite place in the treatment of essehtial-
. , ; hypertension, there is no test or series of tests by which we can measure the chance for a successful.

’ : , result. In order to justify such a procedure, the surgeon must offer a much greater life expectancy .!

AMERICAN' HEART JOURNAL

Nf)6

!h i;; .tritici{K'i!f d from the medical treatment of hypertension. After the various cardiac and,
fimfti(*n u fts have iK-en made, one can usually arrive at an opinion as to whether the patient
,, a K-dc Stir^ira! risk, but the final outcome following operation is difficult to prognosticate.

P.uicnts in vhom the pressure drops the most under sodium amj'tal seem to offer the highest
r»'rcim!ag< of good results. With reference to the question of age at the time of operation, the

rl-mcf of these authors is as follows; in thirty-four cases including both sexes above 50 years
of ace at the time of operation, they found in six-month to three-year follow-ups that twenty-six,
.ir 76 5 cent, were improved, only eight, or 23.5 per cent, were unimproved, and that there
Ri re no de.aths. Tliis compares most favorably with the over-all failure and mortality figure for
S52 c.T^e-s, v.hich was 20.5 per cent.

!>uriug the past four years, 227 patients have been operated upon for essential hypertension
b’. these authors. One hundred fifty-two cases were operated upon by the Smithwick technic
ttith fnllow-ups ranging from six months to three years. The total mortality of this group in
and out of the hospital was 18, or 11.8 percent. There have been thirteen patients, or 8.5 percent,
unimproved. This gives a total of poor results and fatalities of 20.5 per cent to date.

Since June, 1945, these authors have extended the operation to the higher thoracic ganglia
,md have included the ganglLi from the third thoracic to the second lumbar inclusive. 'I'hc
itnrmdi.ite mortality was higher in the more extensive operative procedure. However, jhe
amhors hope the follow-ups will show better end results with a lower late or out-of-hospital
inort-ality.

They grade the severity of the disease in the four major organs involved in essential hyper-
tension. the eyes, cerebral vessels, heart, and kidneys, front 1 to 4 plus. If the degree of involve-
ment in all organs exceeds 8 plus, they believe it is questionable whether a thoracolumbar sym-
pathectomy will give anv lasting results.

Bkixkt.

Grlflith, J. Q., Jr., Padis, N., and Anthony, E.: Selection of Patients With Arterial
Hypertension for Treatment l>y Repeated Injections of Pitressin. .Am. J. M. Se,
21*2: 31 (July), 1946.

Sixty-three persons with hypertension were selected on the basis of (1) positive bio-assay for
aiuidiurctic hormone in scrum; (2) negative bio-assay for gonadotropic hormone in serum at the
level of 3.R1 mouse tinits; (3) normal renal function. It has been previously shown that cases of
this type frequently respond to pituitary irradiation with a disappearance of the antidiuretic
hormone and tlefsniie clinical improvement, the blood pressure often returning to the normal
range. In view of the experience of Robinson and Farr with repeated injections of pitressin, it
was considered probable that this might produce a result similar to that obtained with irradiation.
Variou'. mcihofls of applying this treatment were tried; the one that appeared best was the admin-
iotration of 1 c.c. of pitressin tnnnate in oil weekly for three weeks, then monthly for three months,
and tiiffe ifier rorUtnuing the injections at monthly intervals until the bio-a.ssay for antidiurctic
hornitme IxxMmc and remained negative. Considering the group as a whole, the blood pressure
vas fsgnific-antly lowered and Fj'mptoms improved in about one-half the cases.

When the prtxrcdurc described was used, no reactions except a mild urticaria were ob.serx-cd;
fcten,'’ rc.wtinns <lid occur when aqueous pitressin was employed,

DrR.\M .

K. IL. niti! Scllerx. A. L.:

'Jnly'i.

Tr«,tOHtcrone in Anginn I’octoris. Am. J. M. Sc. 212i 7

Ml?}:

It'-t.nitenme propionate injected intramuscularly and methyl tcsto.sterone administered
anrisilly were found to h.tvc no value in the treatment of angina pectoris. However, tc.stos.
tf'roce prejur uion*- were found to Ire of definite v.alue in relieving the chest discomfort soniciimes
r itii the male climacterium or the similar prerordial ache of ncurorirculatory asthenia
fnroumvrvd in indivsdtwls in the age group commonly subject to .angina pemoris.
to rhc;f of jurcnteral admiiiiss nation of 25 mg. of testosterone projnonate two

SELECTED ABSTRACTS 807 '

to three times weekly \yas found to be preferable to the rather ineffective administration of methyl . 5
testosterone sublingually in doses of 10 to 15 mg. daily. |

. .. Durant. .j

' ... ' . • ' . , /-i

Griffith, G. C., Phillips, A. W., and Asher, C.: Pneumonitis Occurring in Rheumatic ,? .1
. Fever. Am. J. M. Sc. 212; 22 Quly), 1946.

In a group of 1,046 rheumatic fever patients in a United States Naval Hospital, pneumonitis ,
was found in 119 cases. A study of these cases revealed that pneumonitis is one of the prominent f
manifestations of active rheumatic fever. It is defined as a manifestation of rheumatic fever
characterized by an inflammatory process of the lung and pleura, with an insidious onset, migrating |
consolidation, and frequent pleurisy with or without effusion. Occurring in approximately 11 , |

per cent of rheumatic fever cases, it is seen in 53.1 per cent of the acute fulminating type, in 27.4 .
per cent of the polycyclic type, and in 2 per cent of the mild monocyclic type. Depending upon its |
time of appearance in the rheumatic fever state, three types may be recognized: primary acute, , - j
secondary acute, and subclinical. The diagnosis is based entirely on the exclusion of the other . i
, types of pneumonia and the concomitant development of other manifestations of acute rheumatic |

, fever. The roentgen ray findings are not specific, but the rapid shift of the areas of density, the |

rapid development of an effusion, and the close adherence of the density to the bronchovascular , j

markings are helpful findings. Laboratory aids are of little help in establishing the diagnosis, . ' f
The importance of pneumonitis of rheumatic fever origin as one of the serious manifestations of , 1

rheumatic fever activity cannot be overemphasized.

DURANtl .|

, Servelle, M.; Collateral Channels in Venous Obliteration. Arch. d. mal. du coeur. J

39; 2 (Jan.-Feb.), 1946. -.-I

• . 5

5

: The author states that there are few diseases of which knowledge is so limited as in the various ■ i
forms of phlebitis. In reviewing his experiences with obliterative phlebitis of the extremities, ;
he emphasizes the value of venography. This procedure, he points out, establishes a diagnosis , i
which othenvise would be unrecognized until the appearance, years later, of varices, edema, and • ;|

ulceration. I

: After obliteration of a large venous trunk, the circulation may be re-established by collateral ' i

channels developed from the branches of the main trunk or by recanalization. Obliterative phle- , 1
bitis occurs in the femoral veins in 58 per cent of cases, in the popliteal veins in 22 per cent, in the . , -r I
iliac veins in 18 per cent, and in the calf veins in 8 per cent. Venography has demonstrated that
primary varicosities are exceptional; varicosities are much more often secondary to venous obstruc-
tion. This fact explains the danger involved in sclerosing injections and surgical ablations which . '

. are performed blindly. What is commonly called the varicose ulcer is actually, in 80 per cent of .
cases, a postphlebitic ulcer.

Laplace.

.Moses, W. R.; Ligation of the Inferior Vena Cava or Iliac Veins. A Report of 1.36,
Operations. New England J. Med. 235; 2 (July 4), 1946.

1 The clinical differentiation between thrombophlebitis which seldom causes embolism and
phlebothrombosis which commonly causes embolism is often extremely difficult. Various tests

proposed for this purpose are very unreliable, as is phlebography, the popularity of which has de-
clined considerably. . , , , \

;/ In the prevention of embolism from peripheral phlebothrombosis, surgery has many ad-
■ vantages over anticoagulant therapy. The latter may cause serious hemorrhage, especially from*

. a pulmonary infarct or in pregnancy. Second, anticoagulants probably do not affect the clots
already formed but simply prevent their propagation. Third, the time when anticoagulants may "
be discontinued is uncertain. Finally, an anticoagulant usually entails more expense and loss of ; !

tirhe to the patient. . • , ■ .

AMl'RICAN HEART JOURNAL

The- iri'iirafionsadoptcsl for ligniion of the inferior vena cava are thrombophlebitis of the pelvic
I- v.j-l: >aar\’ cfnbolism; pulmonary embolus associated tvich proslatic tenderness of re

"t oncia; ouimonara* infarcts of obscure source; and venous occlusion in the lower extremities
•, ■ ii v.oult! o'.l'.erwise be treated by interruption of the femoral vein alone. Ligation of the
■,cr' . cav « S'; a more effective procedure than ligation of the femoral veins of which it is a comple-
•wft rr'riwr than a substitute. Ligation of the vena cava has an advantage over iliac ligation in
f", (.nting not only from the affected limb, but also from an unrecognized source in the

• -.'-n apparc'iiiy normal limb.

Ihe oper.i’ion involves an extra peritoneal approach, may be completed in ten to fifteen min-
i/e-, an.ii !s attended by a minimum of postoperative discomfort, and complications. Collateral
r-ifi'js return is much more adequate than one would suppose, and edema of the legs is less than
h >1 %\hicli iollowc ligation of the femoral vein. In the author's experience, edema following vena
t-ava ligation has invariably been accompanied by evidence of pre-existence or recurrence of the
process The author reports thirty-five cases; twenty-one ligations of the inferior vena
c.iv.i and fifteen of the iliac vein. (These figures include one case in which both veins were ligated.)
ruder present tentative indications, caval ligation would have been preferable in the fifteen
c’-r.s of iliac lig;ition. Twenty-two patients survived and thirteen died.

Lavlack.

Kempuer, W.; Some* Effects of the Rice Diet Treatment of Kidney Disease Jind Hyper-
tension. Hull. X. V. Acad. Alcd. 22: 358 (July), 1946.

The results of the use of the rice diet in 100 patients with primary kidney disease and in
jiiticnts with hypertensive vascular diseases arc described. The diet is uscrl in an attempt to
iwhice the amount of work required by the kidney cells, and thus reduce their demand for oxygen,
in the presence of a pathologic condition which reduces the supply of o.xygen.

The rice-fruit-sugar diet contains 2,000 calories, of which about 5 Gm. arc fat and 20 Gni.
are protein with not more than 0.2 Gm. of chloride and 0.15 Gm. of sodium. In seventy-nine
nttienis witli hyjiertensive cardiovascular disease, there was an average decrease in serum cholcs-
;erul of SU milligrams.

fn 203 of 322 patients in whom the rice »liet was tried, there was objective improvement.
f)f the 100 i)'itienls with primary kidney disease, 65 per cent were improved. Of the 222 patients
with hypertensive vascular disease, 62 per cent were improved. The author feels that dietary
tre.timcnt .should Ite tried before resorting to sa-nipalhcctomy since the rice diet, if it proves to be
inrmxtivc, ran simply be discontinuerl.

In 100 hypertensive patients studied elcctrocardiographic:illy, there was a return to upright
r w.ivis in eleven of thirty-one [latients with previously inverted T waves. In seventy-seven
o' eighty-.seven pttlents the heart became smaller in size. In ten of the clghty-scvcn patients the
Itcart beramc larger. Forty-four patients who hail papilledema, hemorrhages, or exudates followed
slir rice diet for ta’.o motiths or longer. In all of thent the retinopathy was arrestetl. In twenty
o! the forty-four fcUients, papillctlcma, hemorrhages, or exudates cleared up partially, and in
twenty, f'omt'Ictcly.

XAtim

Tintij. ^mal Nodal Ttieliycardin it» nn Iiifntit. Cardiologia 9: 121, 3; 1945.

Itii* author rerziris the rlinical and pithologic findings in an 11-month-oid child ohservctl
« ter a peruv! of ten uionths. He had three attacks of nodal tachycardia, lasting twenty-threv
forty.'-!'; d iw, and '-evi>n months. Daring the attacks, tite hcetri was markedly crtl.irgpfl,
ilw r.o'e r.u'U'f-l ir-nn ltd) to 2KU per r.'.icute, the blootl pressure was 80/69, and anorexia, wcakncs.s,
pdl-.t, f.y.iws-.;-, edenm, .intl heptomegttiy were present. Between attacks the heart

ft!, are 'uLh;,!--'.! -iiKwn.ttu-JUsiy. 1 he elect rorardiograni taken during an attack showe<! negative
I •- itr.nu'.Li'ely pre;ft|lttg the ORS complexes. Between attacks the P w.it'cs were widened
X-r.ty fiUns tlsowed. tremcuflotis enbrjjemctit of the left \ eiitririe. There was a
■r ’j'*, -r) pi )Kuhr pre tuif no re.spsjnst to quinidine or gyncrgC!) was observeci.

, SELECTED ABSTRACTS .809

- Digilanid Avas given throughout the course of treatment. The child had several bouts of rhino-
pharyngitis, one three months before onset of the tachycardia and others during his stay in the
hospital; Death resulted, froni cardiac failure.

Autopsy revealed an interstitial myocarditis (Fiedler) located exclusively in the right auricle
r in the region where the connecting fibers from the coronary^ sinus (Kung’s Brueckenfasern) join
the Aschoff-Tawara node. The node itself was not involved. The entire conduction system was
free from involvement. Serial sections through the entire heart failed to show other foci of
myocarditis. There was severe dilatation and hypertrophy of all chambers. The nasopharyngitis
. Avas considered the possible etiologic factor of the myocarditis. The importance of serial sec-.

. tipns is pointed out, as only part of the myocardium may be involved. The pathogenesis of the ,,
paroxysmal tachycardia is thought to be an alteration in the close and intimate contact between .
muscle fibers and nen'^e ending.s.

Lenel.

Chapuis, Jcquier-Doze, and Werner; Newer Investigations on the Electrocardiogram
in the Hypoxemic Slate. Helvet. med. acta. 19: 519, 1945.

• Comparisons were made between postexercise and posthypoxemia electrocardiograms in
patients suspected of having coronary’ artery' disease. The authors conclude that changes indica- .
tive of coronary insufficiency will appear following inhalation of gas mixtures with low oxygen
tension, whereas such changes will be lacking in the electrocardiogram following effort. In their -
experience, chest lead CR.j proved to be the best deriv-ation for demonstrating the characteristic
changes. Alterations resulting from sj'mpathetic overactivity provoked by the hypoxemic states •
could be abolished by intravenous injection of DHE (dihydroergotamine). The authors suggest, ,
therefore, that this drug offers a simple means for improving the accuracy of the ‘‘hypoxemia
test” in differentiating changes due to structural cardiac disease from those due to reflex augmenta- .
tions of adrenergic activity.

Wendkos.

. Thompson, L. E., and Gerstl, B.; Thromboangiitis of Pulmonary Vessels Associated
'With Aneurysm of Pulmonary Artery; Report of a Case. Arch. lot. Med. 77; 614
(June), 1946.

This paper reports a case in which an aneurysm of the right pulmonary arteiy' of more than
10 cm. in diameter developed within a period of three months and was associated with thrombo-
. angiitis of both pulmonaiy' arteries and veins. The underlying cause of the changes in the
pulmonary vessels -■\\’as uncertain. Streptococcus viridans infection, syphilis, and congenital ..
malformation were apparently excluded by the clinical course and by the laboratory' and necropsy - .
, observations. The possibility was suggested that the lesions represented a variety of periarteritis
nodosa, but this diagnosis could not be made with certainty.

Bellet.

Westerman, A. : Ou Calcifj’ing, Scarifying Inflammations of the Pericardial Sac, and
the Results of Operative Management, Arch. f. klin Chir. 203; 549 (May 18), 1944.

Fifty-three patients with chronic constrictive and/or adhesive pericarditis who had total
pericardiectomies by Schmieden and medical management by Volhard at the Frankfurt Clinic
; are reported. There were thirty-seven males and sixteen females; the majority were in the second
to fourth decades of life at the time of operation. One-third of thirty'-four patients operated on
before 1939 made complete recoveries; one quarter showed definite improvement. Since 1939
, . .slightly, better results were observed: 64.2 per cent recovered or showed definite improvement^

. Though the immediate operative mortality remains high, it is believed that total pericar-
: diectomy gives much better results than the precordial cardiolysis of Brauer, although the mor-
tality of the latter procedure is much lower at the operating table and even for a year postopera-
^ Lively. Most autopsied cases showed a mixture of the constrictive and adhesh'e forms of chronic

810

•AMERICAN HEART JOURNAL

pericarditis with little or no evidence of active infection. Aschoff bodies were never found and
cultures were always negative, though occasionally histologic tuberculosis was present. The
general impression was of a burnt-out process whose etiology was usually only suggested by the
past medical historj'. This included some acute infection (rheumatic fever, sore throat, grippe,
otitis, or pneumonia) in 68 per cent and tuberculosis in 9.4 per cent. In 19 per cent of the cases
there was no clue as to the etiology.

The various types of acute and chronic pericarditis are described. The clinical picture and
pathologic physiologj^ of the adhesive xariety (accretio cordis) with the systolic rib retraction and
diastolic heart recoil (Brauer’s sign) is distinguished from the constrictive variety (concretio
cordis) with its interference with diastole and resultant venous congestion. However, this differ-
entiation is clear cut more often clinically than pathologically. Both forms affect the function
of the auricles and the right ventricle before the left ventricle, presumably because of the latter’s
thicker walls and higher pressure.

The importance of early operation while the heart muscle retains enough adaptability to
function without its calcific encasement is stressed, as is pre- and postoperativ'e medical care.
The clinical diagnosis was often difficult.

The literature on experimental production of chronic pericarditis and the various forms of
operative interference is reviewed. Pertinent data concerning each of the fifty-three cases are
tabulated, with particular emphasis on the results of the operative procedure.

S.^YEK.

IVlcCutchen, G. T.: Varicositic.s of the Lower Extremity. Am. J, Surg. 72: 63 (July), 1946.

Several methods of e.xamining patients with varicose veins are re-emphasized. The author
also' describes a method for locating incompetent communicating veins or "perforators" as an
operation on the venous system progresses. Patency of the deep venous circulation is determined
by application of a tourniquet at the upper thigh for the great saphenous vein and just below the
knee for the lesser saphenous. The tourniquet is applied with the patient in the upright position
so that the veins are distended at the beginning of the lest. The patient is allowed to walk a
few steps. If the veins become less tense, the deep circulation is patent.

The method of locating incompetent communicating veins during an operation consists in
placing the patient in the reverse Trendelenburg position (legs and trunk down) and advancing a
tourniquet from below upward on the leg. At the points where perforators are suspected, the vein
is exposed and severed between clamps. The perforator, if it is found, is treated in the same
manner. Preliminarj' testing may be carried out by the application of two tourniquets at short
distances from each other while the Trendelenburg position is assumed, followed by assumption
of the reverse Trendelenburg position. However, it is believed that the ligation as described acts
in a more effective manner than the lower tourniquet in stopping confusing flow from the distal
points of the vein. A number of illustrations accompany the description of this method.

The extreme reverse Trendelenburg position should be assumed and maintained for five to
ten minutes after all ligations are completed. If dilatation of any of the veins becomes manifest
it may be assumed that an incompetent perforator has been overlooked and further search is
in order.

N.vide.

Gosgrove, Jr., C. E., nnd Katiinp, D. IL: Endoenrdini Sclerosi.s in Infants a»id Children.

Am J. Clin. Path. Ifi: .322 (May), 1946.

The authors review the theories of the pathogenesis of endocardial sclerosis in infants anti
children and de^scribe the pathologic findings listed by other observers. These findings are also
comparer! with the findings in six cases of their own. Composifeb’ these varied gros.sly from
simple thickening and opacity of the endocardium to severely distorted vah'cs in e.Ntrcnie in-
st.anres. Th.c myocartiial changes seemed to parallel the extent of the endocardial involvement.
The Inxtrt generally was enlarged due to myocardial fibrosis, myocardial hyqicrtrophy, and dila-
tation of tlsc ventricles. The coronary’ arteries were normal.

- SELECTED ABSTRACTS ' 811

Microscopically the endocardial thickening was composed chiefly of collagenous connective
tissue with some increase in elastic tissue, which in many areas extended as fingerlike projections
between the myocardial fibers. Occasionally the thickening was nodular and reserhbled myxo-
inatous tissue or possessed a cartilaginous-like component at the base of the valves. Occasional
vessels in the endocardium showed much narrowing due to endothelial fibrosis. The myocardium
.frequently was markedly vascular and showed numerous areas of degeneration, varying from loss
of muscle striation to necrosis. In none of the six cases was there definite indication of inflam-
matory changes as evidenced by myocardial giant cells or infiltration with lymphocytes or poly-
nrorphdnuclear cells. The myocardial changes were particularly prominent in the papillary
muscles and less frequent in the ventricular septum. Except for the Thebesian vessels, the veins
of the myocardium were generally normal and no thromboses were found. When myocardial
lesions occurred, they resembled infarctions rather than inflammatory lesions. This, together
with the relative or complete occlusion of the smaller mural arterial and venous channels, inclined
the authors to accept the probability that primary endocardial sclerosis is congenital. This
impression was strengthened by the absence of evidences' of inflammatory cell infiltration, the
marked edema, the relatively young connective tissue, the lack of advancing proliferation of con-
nective tissue, and the minimal tendency toward vascularization. Because of the high proportion
of recorded illness in the mothers of these infants, the authors suggest that such illnesses of the
mother during pregnancy, particularly early pregnancy, may be a factor in the production of endo-
cardial sclerosis.'

They conclude that the gross and microscopic characteristics of the lesions indicate that
endocardial sclerosis in infants is a form of congenital heart disease.

Meranze.

Estes. J. E., and Keith, N. : Hypothyroidism and Mild Myxedema from Thiocyanate Inr
toxication. Am. J. Med. 1: 45 Quly), 1946.

Thiocyanate therapy in a 62-year-old woman with hypertension caused definite symptoms,
of hypothyroidism and mild myxedema. Cardiac enlargement, demonstrated by roentgeno-
graphic. examination, regressed upon withdrawal of the drug. During thiocyanate intoxication
the electrocardiogram displayed an abnormally low total voltage of the QRS complexes and
inverted, diphasic, and isoelectric T waves in various leads. The QRS complexes reverted to
normal total voltage and the T waves became upright and of normal amplitude in all leads upon
recovery -from the intoxication.

' The ultimate effects of hypothyroidism upon the heart are discussed. The cardiac enlarge-
ment seen in the teleoroentgenogram is generalized, involves all four chambers, and is currently
.viewed as a dilatation rather than a hypertrophy or pericardial effusion. The electrocardio-
graphic changes are attributed to a reduction in cardiac conductivity rather than to reduction in
skin conductivity.

^ . Friedland.

Stewart, H. J., Evans, W. F., Brown, H. and Gerjuoy, J. R.: Peripheral Blood Flow,
Rectal and Skin Temperature in Congestive Heart Failure; The Effects of Ranid
Digitalization in This State. Arch. Int. Med. 77: 643 (June), 1946.

It has been observed by various investigators that the temperature of the surface of cardiac
patients is lower than in normal individuals, while that of patients with infectious fever is higher
than normal. Certain experimental data point to a decrease in the amount of blood allotted to
the peripheral blood flow in congestive heart failure.

Peripheral blood flow was measured in fifteen patients exhibiting congestive heart failure
, before and after administration of strophanthin K and digitaline Nativelle intravenously ' Meas
urements of rectal and of skin temperature were recorded. Electrocardiograms circulation time'
and venous pressure were made to correlate with the measurements of the peripheral blood flow'
It tras 0 bset%.ed that the amount ot blood flow allotted for the whole periphery o the body is
w,th.a the normal range dunng heart failure as compared with the amount in norLi iubiec^^s at

AMERICAN HEART JOURNAL

«I2

the Kinic ernironniental tempeniiure. Even though the same amount of blood is allotted to the
t'criphcrai circulation in heart failure, it is insufficient because of its slowed velocita- in a vascular
tree that is ddateri to maintain an adequate elimination of heat in the face of the metabolic dc-
tnan‘i=, so that the interna! temperature of the body (rectal temperature) rises.

After the administration of strophanthin K intravenously, the peripheral blood flow increases.
\\ ith the allocation of more blood to the peripher>-, the temperature of the skin rises and the body
rin now lose more heat by way of the skin, and its internal temperature {rectal temperature)
falls slightly but does not usually reach normal levels over the intervals studied by the author.

Bfli.et.

lladner. S. : An Attempt at the Ilocntgcnologic Viswnlization of Coronary Blood Vessels
in IMan. Acta, radiol. 26: 497 (No. 6), 1945.

Using a modified technique of sternal puncture, a needle was inserted into the anterior upper
medinstinum and then, under fluoroscopic guidance, into the ascending aorta. Twenty to 30 c.c.
of thorotrast solution were injected rapidly. Five patients were studied by the technique. Of
films taken in three cases, onlj' one proved satisfactory'. This film is reproduced and shows
the aortic valves, the dye in the sinuses of Valsalva, and \’ague shadows of what appear to be the
first [lortions of the coronary' arteries. One patient developed mediastinal emphy'sema, and in
one the needle penetrated the posterior aortic wall so that thorotrast was deposited in the peri-
cardium, setting up a purulent inflammation which only very gradually resolved. At present, the
prnlilem of a satisfactory contrast medium has not been adequately' solved.

Sayek.

Lniidis, E. INI., Brown, E., Fauleanx. M., and Wise, C.; Central Venous Pressure in Re-

Intiun to Cairdiac “Competence,” Blood A'olumc, and Exercise, J. Clin. Investigation
25: 237 (March), 1946.

Evidence was obtained in anesthetized dogs to support the "back pressure” hy'pothesis of
congestive heart failure. The dogs were c.\crcised by’ electrical stimulation of all four limbs once
each second. During control exercise, while cardiac function was normal, venous (right auricular)
firessiirc, after a transient rise, fell to 96 mm. of water. After ligtUion of coronary' arteries, resting
venous pressure did not rise, but exercise was accompanied either by' a decline in venous pressure,
v.hich was always less pronounced than that obserx-cd during control exercise, or by a definite rise.
Iflectricaliy induced auricular fibrillation caused only slight rises in venous pressure, whereas
combined auricular fibrillation plus exercise elevated venous pressure to higher levels. On the
contniry, elex-atcd resting venous pressure due to cardiac tamponade was lowered by exercise
.as in the control experiments, un!e,ss prior myocardial damage had reduced cardiac competence.
.Moreover, when venous pressure had been increased to extremely high levels by infusions of
citrated whole blood or of Ringer’s solution amounting to 50 per cent or more of the calculated
blood volume, exercise xwis still capable of reducing the venous pressure.

A final set of e.xpcrinicnis showed that during aspliycxia, agonal arterial constriction elTccted
a rctlistribution of apfiroximatcK' 20 per cent of the total circulating blood volume from the
arterial to the x enou.s bed. After auricular fibrillation and prolonged exercise, the blood redis-
tributed to ihe venous bed during asphyxia amounted to about one-half the usual quantity,
indicating that filtnition fiad occurred during the high venous pressure incident to the conihina-
tion of auricular fibrillation and exercise.

Tlicse experimental data provide the fundamentals for the development of a hyjKilhesis of
clirortic congestive failure basetl ujmn the "back prc.ssurc” concept. Patients with reduced cardiac
romiM;rC!tttr develop increased venous pressure during muscular activity. KfTective circulating
blivji! vrslunie iiiminisht-s consequent to both sequestration of blood in the venous system and ex-
ct"i*ive fihraiioii. Compensatory va.soconstriction occurs tind is .accompanied by’ reduced renal
cf.crcthm f‘i srKlitirn and water and overproduction of cry’tbrocytes and plasma proteins. Re-
p-atc-d mt!<cuhf .ictsvity leads to sc-i'ond.iry plethora or hypervolemia and cve-ntuates in the
typ'C.ilty higft testing tenous pressure of chronic congestive failure.

FjtlEm.ANP.

{

Book Reviews

. Le Tumeurs et les Polypes du Coeur — Etude Anatomo-Clinique: By Dr. Ivan Mahaim.

’ . ; Monographie de Tlnstitut d’Anatoniie pathologique de I’Universite de Lau.sanne. F. Roth.et
Cie, Editeurs, Lausanne; Masson et Cie, Editeurs, Paris, 1945. With 568 pages and 67 '■
illustrations.

; , This book includes an exhaustive description and extensive discussion, with a fairly complete

bibliography, of cases of primary and secondary tumors of the heart and pericardium. 'The
author draws attention to the more frequent occurrence of these tumors than has been recognized". -
hitherto bj^ most clinicians or even many pathologists. He gives in detail the clinical signs and
symptoms that should lead to a premortem diagnosis of these tumors, expecially in certain loca-.
tions, and emphasizes the importance of considering this diagnosis in all cases of otherwise un- •
explained cardiac insufficiency. Much attention is paid in this book to the subject of polypoid , .
growths, especially those within the left atrium or auricle, some of which are not trulj'^ neoplastic. "
The benign polyps are the subject of e.xtensive description and discussion, because the author , . .
believes that thej’’ ma}' kill by obstructing the flow of blood from atrium to ventricle, either by ,
valvular occlusion, or by atrial obliteration, and that a cure might be effected by surgical removal •

- ; of these growths. In his opinion these tumors olTer a challenge to the surgery of the future, and. , ,
T . he even gives in detail the possible techniques that have occurred to him! The possibility of sucr - '

, cessful excision of some tj'pes of tumor of the pericardium is also considered. .

: . The occurrence of embolism associated with intracardiac growths, especially of the polj'poid .
type, is emphasized, and the author draws attention to the importance of embolectomy in cases , •

' ; of peripheral embolism. Such emboli are accessible to biopsy or removal, and Histologic exami-
- nation of the embolus can prove to be a great aid in the diagnosis of intracardiac tumors. In
: ' , his experience, my.xoraatous tissue in a peripheral embolus in the systemic circulation means,-. .

; almost unquestionably, the existence of a polyp in the left atrium or auricle; thrombotic tissue
.may mean a thrombotic l^olyp or myxomatous polyp covered with thrombus at the tip, or. a
’ , miiral thrombus in the left atrium, or, much less likely, in the left ventricle. He gives in full,

detail the clinical signs of an obstructive mass in the left atrium but states that there are no
. certain signs of an occlusive polyp in the right atrium. Particular emphasis is placed on the im- . ■

portance of basic simple clinical observations, and the inadequacy of some of the special and . '
more expensive methods of investigation, for the purpose of the clinical diagnosis of tumors of '
heart and pericardium. ^

, The book is well written and covers very thoroughly the description and discussion of all the- .

' known benign and malignant tumors of both heart and pericardium. It is an important and
timely contribution to this subject and certainly constitutes a challenge to those who are inter-
, , ested in heroic surgery. It is his hope that, while surgeons are learning techniques for the possible

; , excision of many of these tumors, physicians will busy themselves with learning how to make
an early clinical diagnosis of what he considers an important cause of cardiac insufficiency. . - ,

Harry Goldblatt.

S13

American Heart Association, Inc.

1790 Broadway at SSth Street, New York, N. Y.

Or. Rov W. Scott
Pusidenl

Dr. Howard F. West
Vicr~Presider.t

Dr. George R. Herr.man'n
Treasurer j

Dr. Howard B. Sprague
Secretary

BOARD OF DIRECTORS

Dr. Edgar V. Allen Rochester. Minn.

Dr. Graham Asker Kansas City. Mo.

•Dp.. Arlie R. Barnes Rochester, Minn.

Dr. .Alfp.ed Blalock Baltimore

*Dr, William H. Bunn Voungstown. Ohio

Dr. Clarence de la Ciiapelle. .New York City

•Dr. Tinsley R. Harrison Dallas

Dr. George R. Herr.mann Galveston

Dr. T, Duckett Jones Boston

Dp. Louis N. Katt Chicago

Dr. Samuel A. Levine Boston

Dr. Gilpert Marouardt Chicago

•13r. H. M. Marvin New Haven

•Dr. Kdwk P. Maynard. Jr Brooklyn

•Dr. Thomas M. McMillan philadelohla

Dr. Jo.natiian Meakins Montreal. Can.

Dr. E. Sterling Niciiol Miami

♦Executive Committee.

Dr. Harold E. B. Pardee New York City

Dr. William B. Porter .Richmond, Va.

♦Dr. David' D. Rutstein New York City

♦Dr. John J, S.\MrsoN San Francisco

Dr. Roy W. Scott Cleveland

♦Dr. Howard B. Sprague Boston

Dr. George F. Strong.. .Vancouver, B. C., Can.

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Dr. Homer F. Swift New York City

Dr. William P. Tho.mpson ,Los x\ngelcs

Dr. Harry E. Ungerleider New York City

♦Dr. Howard F. West Los Angeles

Dr. Paul D. White Boston

Dr. Frank N. Wilson Ann x\rbor

♦Dr. Irving S. Wright New York City

Dr. Wallace M. Yater Washington, D. C.

Dr. H. M. Marvin, Acting Executive Secretary
Anna S. Wright. Ofiee Secretary
Telephone, Circle S-8000

American Heart Association is the only national organization devoted to
-*■ educational work relating to diseases of the heart. Its activities arc under the
control and guidance of a Board of Directors composed of thirty-three eminent phy-
sicians who represent ever}' portion of the country.

A central office is maintained for the coordination and distribution of important
information. From it there issues a steady stream of books, pamphlets, charts, films,
lantern slides, and similar educational material concerned with the recognition, pre-
vention, or treatment of diseases of the heart, which are now the leading cause of death
in the United States. The American Heart Journal is under the editorial super-
vision of the Association.

The Section for the Study of the Peripheral Circulation was organized in 1935
for the purpose of stimulating interest in investigation of all types of diseases of the
blood and lymph vessels and of problems concerning the circulation of blood and lymph.
Any physician or investigator may become a member of the section after election to
the '\merican He.art Association and payment of dues to that organization.

The income from membership and donations provides the sole financial support
of the Association. Lack of adequate funds seriously hampers more intensive edu-
cational activity and the support of important investigative work.

Annual membership is $5.00. Journal membership at $11.00 includes a year'.s
subscription to the American Heart Journ.\l (January'- December) and annual mem-
bership in the Associ.nion. The Journal alone is $10.00 per year.

Tiic AscQci.ation earnestly solicits your support and suggestions for its work.
Me'nbrrshtp ap.nlicttion b!ank< wall l>e sent on request. Donations wall be gratefully
reedvM and promptly acknowledged.

American Heart J ournal

For the Study of the
CIRCULATION

©Am. Ht. Assn.

Published Monthly
Under the Editorial Direction of
THE AMERICAN HEART ASSOCIATION
■ Thomas M. McMillan

Ediior-in- Chief

ASSOCIATE EDITORS

Wallace M. Yater
Samuel Bellet
Louis B. Laplace

EDITORIAL BOARD

Edgar V. Allen
Alfred Blalock
Clarence E. de la Chapelle
Harry Goldblatt
Tinsley R. Harrison
T. Duckett Jones
Louis N. Katz
Eugene M. Landis

John K. Lewis
H. M. Marvin
Jonathan C. Meakins
Roy W. Scott
Isaac Starr
Paul D. White
Frank N. Wilson
Charles C. Wolferth

Irving S. Wright

VOLUME 32
JULY-DECEMBER, 1946

St. Louis

THE C. V. MOSBY COMPANY
1946

Copyright 1946, By The C. V. Mosnv Company
{All rights reserved)

Prill (od in llie
United States of America

Press of

The C. V, Moshy Compatty
St. Louis

INDEX TO VOLUME 32

✓

AUTHORS INDEX

A

.. Abramson, David I., Lerner, David, Shu-
MACKER, Harris B., Jr., and Hick,
Ford K. Clinical picture and treat-
, - . • ment of the later stage of trench

foot, 52

. Alexander, Howard. (See Simonson, Aiex-
. , ander, Henschel, and Keys), 202

Alture-Werber, Erna. (See Loewe, Rosen-
blatt, and Alture-Werber), 327
Anderson, Milton W., Barker, Nelson W.,
AND Seldon, Thomas H. A clinical
. . , evaluation of powdered human blood

cells in the treatment of ulcers of the
extremities associated with vascular
disorders, 754

B

Baer, Samuel. (See Loewenberg and Baer),
653

Baldwin, Eleanor deF., Moore, Lucille V.,
Noble, Robert P. (with technical as-
sistance of Patterson, Michaeleen,
and Harnsberger, Doris M.). The
demonstration of ventricular septal
defect by means of right heart cathe-
terization, 152

Barker, Nelson W. (See Anderson, Barker,
and Seldon), 754

. Barker, Paul S. (See Wilson, Johnston, Ros-
enbaum, and Barker), 277
. Beaser, S. B., and Rodriguez-Molina, R.

Electrocardiographic changes occur-
ring during treatment with fuadin so-
lution, 634

Beissinger, . Heinz F. (See Weinberg and
Beissinger), 665

.: Bembenista, J. K. Cor bilocuiare, 394

BiorckJ Gunnar, Anoxemia and exercise
tests in the diagnosis of coronary dis-
ease, 689

•Bland, Edward F. Rheumatic fever and
rheumatic heart disease in the North
African and Mediterranean Theater
of Operations, United States Army,

"'.',•545

; Boyer, Norman H. (See Nay and Boyer),

• 222 -

^ Brown, N. Worth. (See Ellis and Brown),

Burch, G. E. Influence of variations in atmos-
pheric temperature and humidity on
. - , ' , the rates of water and heat loss from
the respiratory tract of patients with
, . • . ' congestive heart failure living in a

subtropical climate, 190

. The rates of water and heat loss from -

the respiratory tract of patients with ..
congestive heart failure who were from;
a subtropical climate and resting in a - ■

comfortable atmosphere, 88

, and Kimball, J. LeRoy. Notes on the ,

similarity of QRS complex configura- =
tions in the Wolff-Parkinson-M%ite
syndrome, 560-

Butterworth, Scott, and Poindexter,
Charles A. The esophageal electro-
cardiogram in arrhythmias and tachy-
cardias, 681

C

Cathcart, Richard T. (See Spain and Cath- , ' ,
cart)., 659 ‘ „ ;

Clark, Mardelle L. (See Eanes, McGill, and
Clark), 504

CoFFEN, Charles W., and Scarf, MaxwelL; :

Acute pericarditis simulating cord- ■ • '
nary artery occlusion, 515 . '

Coombs, F. S. (See Warren, Higley, and N
Coombs), 311

D ,

Delevett, Allen F., and Poindexter,

Charles A. Plasma concentrations - . -
of quinidine with particular reference ' ,
to therapeutical^ effective levels in . - -

two cases of paroxysmal nodal tachy- , .
cardia, 697 .

DiPalma, Joseph R., and MaGovern, John
J. Disadvantages of thiouracil treat-
ment of angina pectoris, 494 •

Donovan, Maurice A. Pain of unusual dura- '
tion due to progressive coronaiy^ oc-.
elusion with associated mediastinal '

tumor, 786 , . :

E ■' .'

Eanes, Richard H., McGill, Kenneth H.,.

and Clark, Mardelle L. Cardio- •.

vascular defects in Selective .Service

registrants, 504

Eidlow, S., and Mackenzie, Eleanor, R.
Anomalous origin of the left coronaiy
artery from the pulmonary artery ; . y.
report of a case diagnosed clinically
and confirmed by necropsy, 243 * - .

Ellis, George M., and Brown, N.- Worth. - .
Parasternal leads , in tricuspid insuf-
ficiency, 364

S15

AUTHORS INDEX

SIC)

F

I‘A«:inLO. J. C. [Sec Suarez, Fasciolo, and
Taquini), 339

. (See Taquini and Fasciolo), 357

Fi i ton, Frank T. fAVr Zimdahl and Fulton),
117

G

GnionR, Arthur J., and Goerner, Jessamine
R. A simplified and more standard-
ized technique for recording multiple
precordial electrocardiograms, 163

Guknandt, B,, and Nylin, G. The relation
between circulation time and the
amount of the residual blood of the
heart, 411

Goerner,^ Jessamine R. [Sec Geiger and
Goerner), 163

Grant, Harold. [See Reichsnian and Grant),
43S

, and Reichsman, Fr,\ncis. The effects of

the ingestion of large amounts of so-
dium chloride on the arterial and
venous pressures of normal subjects,
704

Greene. Ralph C. Combined sulfonamide
and diphtheritic myocarditis in cuta-
neous diphtheria, 250

H

Harken, Dwight E., and Zoll, Paul M. For-
eign bodies in and in relation to the
thoracic blood vessels and heart. HI.
Indications for the removal of intra-
cardiac foreign bodies and the be-
havior of the heart during manipula-
tion, 1

Harnsherger, Doris M. [See Baldwin,
Moore, Noble, Patterson, and Harns-
berger), 152

Harris, Raymond. [See Scherf and Harris),
443

Hecht, Hans H. Potential variations of the
right auricular and ventricular cavi-
ties in man, 39

Hr-NSCHEL. Austin. (Ncc Simonson, .Ale.xander,
Henschel, and Keys), 202

Heyer, Howard E. Abnormalities of the
respiratory pattern in patients with
cardiac dyspnea, 457

Hick, Ford K. (See Abramson, Lerncr, Shu-
raacker, and Hick), 52

Higi.ey, C. S. [See Warren, Higlcy, and
Coombs), 311

Hill. R, F. The construction of the cardiac
vector, 72

Hunt, Homer H., and Weller, Carl V. The
syndrome of alxlominal aortic ancu-
ry.-.m rupturing into the gastrointes-
lin.al tract, 571

J

JosiNsinN, !• R.^NKi.tN D. [See Rosenbaum,
Wilson, and Johnston), 135
iSee Wit«o{t, Johnston, Rosenbaum, and
Barker). 277

Jones, Retcroy H., Jr., and Moore, Wil-
liam W. Purpuric manifestations of
rheumatic fever and acute glomerulo-
nephritis, 529

K

Keys, Ancel. [See Simonson, Ale.xander,
Henschel, and Keys), 202

Kimball, J. LeRoy. [See Burch and Kim-
ball), 560

L

Lerner, David. [See Abramson, Lerner, Shu-
raacker, and Hick), 52

Lindsay, Stuart. The heart in primary sys-
temic amyloidosis, 419

Littmann, David. Persistence of the juvenile
pattern in precordial leads of healthy
adult Negroes, with report of electro-
cardiographic surv'cy on three hundred
Negro and two hundred white sub-
jects, 370

, and Tarnower, Herman. WolfT-Park-

inson-White syndrome, 100

Loewe, Leo, Rosenblatt, Philip, and Al-
ture-Werber, Erna. a refractory
case of "subacute bacterial endocarditis
due to VeilloncUa gazogenes clinically
arrested by a combination of peni-
cillin, sodium para-aminohippurate,
and heparin, 327

Loewenberg, Samuel A., and Baer, Samuel.
Aneurysm of the descending thoracic
aorta, 653

Loube, Samuel D. [See Manchester and
Loube), 215

M

McGill, Kenneth H. [See Eanes, McGill, and
Clark), 504

MaGovern, John J. [See DiPalma and Ma-
Govern), 494

Mackenzie, Eleanor R. [Sec Eidlow and
Mackenzie), 243

Manchester, Benjamin, and Louiuw Samuel
D. The velocity of blood flow in nor-
mal pregnant women, 215

Master, Arthur M. Right-sided aorta with
atypical coarctation involving only
the left subclavian artery'; hyperten-
sion, 778

Miller, Isidore. [See Russek, Rath, Zoh-
nian, and Miller), 468

Moore, Lucille V. [See Baldwin, Moore,
Noble, Patterson, and Harnsberger),
152

Moore, William W. [See Jones ,nnd Moore),
529

de Moura, Jose Proenca Pinto. Complete
auriculoventricular block and bundle
branch block with intercurrent auric-
ular flutter, 794

N

Kay, Richard M., and Boyer, Norman H.
Acute pericarditis in voting adults. 222

Noble, Robert P. [See finldwin, Moare,
Noble, Patterson, and Harnsberger),
152

AUTHORS INDEX 817 ;

• Norris, Robert F., and Pote, Harry H.

■ Hypertrophy of the heart of unknown
• ^ etiology in young adults: report of
four cases with autopsies, 599
Noth, Paul H. Electrocardiographic patterns
in penetrating wounds of the heart,
,, '-713

, , Nylin, G. (See Gernandt and Nylin), 411

'•S.V-'' ' ' o

. Oyster, Joseph M. (5ee Tandowsky, Oyster,

' , and Silverglade), 617

P

' .Patterson, Michaeleen. (See Baldwin,

. Moore, Noble, Patterson, and Harns-

, ' berger), 152

Paull, Ross. The neurovascular syndrome as
. manifested in the upper extremities,

32.

Penner, Sidney L. (See Peters and Penner),
645

Peters, Michael, and Penner, Sidney L.

Orthostatic paroxysmal ventricular
tachycardia, 645

Poindexter, Charles A. (See Butterworth
and Poindexter), 681

^ , . (See Delevett and Poindexter), 697

, Pote, Harry H. (See Norris and Pote), 599

Q

Quinn, Robert W. The incidence of rheu-
matic fever and heart disease in school
children in Dublin, Georgia, vlth some
epidemiological and sociological ob-
servations, 234

R

Rath, Maurice M. (See Russek, Rath, Zoh-
man, and Miller), 468

Reichsm-A-N, Francis. (See Grant and Reichs-
man), 704

, and Grant, Harold. Some obsers'ations

on the pathogenesis of edema in car-
diac failure, 438

, RodriQUEZ-Molina, R. (See Beaser and Rod-
riquez-MoIina), 634

, . Rogers, H. Milton. Bilateral pulmonary in-
farction and pneumothorax compli-
cating hypertensive, coronary heart
disease with myocardial infarction :
report of a case, 519

Rosenbaum, Francis F. (5ee Wilson, Johns-
ton, Rosenbaum, and Barker), 277

-, Wilson, Frank N., and Johnston,

Franklin D. The precordial electro-
cardiogram in high lateral myocardial
infarction, 135

. Rosenblatt, Philip. (See Loewe, Rosen-
blatt, and Alture-Werber), 327

- , Russek, Henry I., Rath, Maurice M,, Zoh-

, , MAN, , Burton L., and Miller, Isi-

dore, The influence of age on blood
, ■ • pressure, 469

Rytand, David A. An auricular diastolic.miir-
mur with heart block in elderly na-
tients, 579

Scarf, MAXtTOLL. (See Coffen and Scarf), 515
ScHERF, David, and Harris, Raymond. Goro- ■
nary sinus rhythm, 443

ScHLicHTER, J. G. Studies on the vasculariza-
tion of the aorta. I. The vasculari- _ ■
zation of the aorta in the normal dog, ,
770

Seldon, Thomas H. (See Anderson, Barker,
and Seldon), 754

Shumacker, Harris B. (See Abramson, Ler- , ,
ner, Shumacker, and Hick), 52 ,

Silverglade, Alexander. (See Tandowsky,
Oyster, and Silverglade), 617
Silverman, Jacob J. The incidence of palpa-
ble dorsalis pedis and posterior tibial
pulsations in soldiers, 82
Simonson, Ernst, Alexander, Howard, Hen- ;

scHEL, Austin, and Keys, Ancel; . ; .
The effect of meals on the electror ;
cardiogram in normal subjects, 202 •
Smith, Leslie B. Paroxysmal ventricular , -
tachycardia followed by electrocardio-
graphic syndrome, 257

Spain, David M., and Cathcart, Richaru T. ;
Heart block caused by fat infiltration
of the interventricular septum ,.(cor .
adiposum), 659

Suarez, J. R. E., Fasciolo, J. C., and Ta-
QUINI, A. C. Cardiac output in heart,
failure, 339

Suarez, Ramon M., and Suarez, Ramon M., - -
Jr. The T wave of the precordial . ’
electrocardiogram at different . age ; -
levels, 480

Suarez, Ramon M., Jr. (See Sudrez and ’
Sukrez, Jr.), 480 ' ,

Swenson, Roy E. Parenteral vitamin B as an
agent for determining the arm-to-,
tongue circulation time, 612 ;

T

Tandow'sky, Ralph M., Oyster, Joseph M., ''

AND Silverglade, Alexander. The
combined use of lanatoside C and
quinidine sulfate in the abolition of ..-
established auricular flutter, 617
Taquini, a. C. (See Suarez, Fasciolo, and
Taquini), 339

, AND Fasciolo, Juan Carlos. Renin in '

essential hypertension, 357
Tarnower, Herm.\n. (See Littmann and:" v
Tarnower), 100

W ■

Warren, Harry A., Higley, C. S., and ’
Coombs, F. S. The effect of salicylate
on acute rheumatic fever, 311
Weinberg, Tobias, and Beissinger, Heinz F.

Syphilitic gummatous aortitis as the '
cause of coronary artery ostial stenosis

and myocardial infarction, 665
Weller, Carl V. (See Hunt and Weller), 57l ■

Wilson, Frank N. (See Rosenbaum, Wilson, ■

and Johnston), 135 . V

AUTHORS INDEX

^ IO!!Ns70S. FRAVKLIX D., RoSKNHAUM,

Fkancis F., a.vd Rarkkr, Paul S.
On Finthoven's triangle, tiie theory of
iinii>til.ir elect rocardiographic leads,
.'Uid the interpretation of the precor-
(iial decirocanliogram. 277

\\K!Gi!r. S Experiences with dicunia-

rol 13,3* met hyiene-bis-14-hydroxycou-
marinl) in the treatment of coronar>'
thromlxtsis with myocardial infarc-
tion, 20

! Young, Dennison. Electrocardiographic
, changes occurring during tippler respi-

I ratory infections, 383

ZiMDAiiL, Walter T., and Fulton, Frank T
Transient ventricular fibrillation, 1 1
ZoiiMAN, Burton L. {See Russek, Rath, Zoh-
man, and Miller), 468
ZoLL, Paul M. (See Harken and Zoll), 1

”^1 I

SUBJECT INDEX

A

Abdpminal aortic aneur\’sm rupturing into gas-
trointestinal tract, syndrome of
(Hunt and Weller), 57i
, aortography, retrograde, 406*

Abnormalities of respiratorj'^ pattern in patients
with cardiac dyspnea (Heyer), 457
Acetylcholine, stimulating action of, on heart,
408*

Acute pericarditis in young adults (Nay and
Boyer), 222

Addison’s disease, disturbance of pacemaker
and of conduction in, 270*

Adults, young, acute pericarditis In (Nay and
Boyer), 222

African, North, and Mediterranean Theater of
Operations, United States Army,
rheumatic fever and rheumatic
heart disease in (Bland), 545
Age, influence of, on blood' pressure (Russek
et al.), 468

levels, different, T wave of precordial electro-
cardiogram at (Suarez and Suarez,
Jr.), 480

Albumin, human, concentrated, in treatment of
shock, 672*

Alcohol in treatment of angina pectoris, 403*
American Heart Association, expanded pro-
gram of, for 1947, 679
Amyloidosis myocardii, 127*

systemic, primary', heart in (Lindsay), 419
Anemia, cardiovascular system in, with note
on particular abnormality of sickle
cell anemia, 270*

Aneurysm, aortic, abdominal, rupturing into
gastrointestinal tract, syndrome of
(Hunt and Weller), 571
arteriovenous, following surgical operations,
805*

of descending thoracic aorta (Loewenberg
and Baer), 653

ventricular, longevity with; report of case
with survival period of fifteen years,
402*

Aneurysms, traumatic, of extremities, 407*
Angina pectoris, alcohol in treatment of, 403*
application to study of; circulator)" changes
following injection of hypertonic
saline solution, 129*

disadvantages of thiouracil treatment of
(DiPalma and MaGovern), 494
life expectanc)" in, 269*
testosterone in, 806*

Announcements, 133

Anoxemia and- exercise tests in diagnosis of
coronar)" disease (Biorck), 689
experirnental c)’'anosis and, effects of artificial
ductus arteriosus on, 407*

*An asterisk (*) after a page number indicates
article.

Aorta, right-sided, with atypical coarctation in-
volving only left subclavian artery;
hypertension (Master), 778'
roentgenological picture of coarctation of,
and its anatomical basis, 127*
slowly progressive occlusive thrombosis of
abdominal portion of, 127*
studies on vascularization of; I. Vasculariza-
tion of aorta in normal dog (Schlich-
ter), 770

thoracic, descending, aneruysm of (Loewen-
berg and Baer), 653

Aortic aneurysm, abdominal, rupturing into
gastrointestinal tract, syndrome of
(Hunt and Weller), 571
coarctation, new indirect radiologic sign in
diagnosis of, by means of superior
retrograde aortography, 274*
perforation secondar)" to carcinoma of esoph-
agus, genesis of, 674*

stenosis due to calcified syphilitic valvulitis
403*

valve, bicuspid, diagnosed during life, 401*
valves, rupture of, due to effort, 273*

Aortitis, gummatous, syphilitic, as cause of
coronar)" artery ostial stenosis and
myocardial infarction (Weinbertr
and Beissinger), 665

Aortography, abdominal, retrograde, 406*
retrograde, superior, new indirect radiologic
sign in diagnosis of aortic coarcta-
tion by means of, 274*

Arm-to-tongue circulation time, parenteral
vitamin B as agent for determining;
Part I (Swenson), 612

Army, United States, rheumatic fever and rheu-
matic heart disease in North African
and Mediterranean Theater of Op-
erations (Bland), 545

Arrhythmias, acute, treatment of, during anes-
tbesia by intravenous procaine,

and tachycardias, esophageal electrocardio-
gram in (Butterworth and Poindex-
ter), 681

Arterial and venous pressures of normal sub-
jects, effects of ingestion of large
amounts of sodium chloride on
(Grant and Reichsman), 704
disease, peripheral, 125*
pulse pressure, relation of, to arteriovenous
oxygen difference, especially in arte-
rial hypertension, 126*

Arteriosclerosis obliterans, relation of tobacco

diabetes mellitus,

400*

Arteriovenous aneurysm following surgical op-
erations, 805* /

the reference is an abstract and not an ori«'inal

SUBJECT INDEX

.S2l*

.Xrteriovcnou' — Cont'd

r>.xv£;fri difTfrenre. relalion of arterial pulse
pressure to, especially in arterial
iiypertcnsion, 126*

Aitcritis. !cni[soral. };ener;dized vascular dis-
ease, 406*

Aric-ry. coron.ary, left, anomalous origin of,
from pulmoiuirx' arterx-; report of
ease diagnosed clinically and con-
firmed by necropsy (Eidlow and
Mackenzie), 243

occlusion, acute pericarditis simulating
(Codon and Scirf), 515
ostial stenosis and myocttrdial infarction,
syphilitic gummatous aortitis as
cause of (Weinberg and IBeissingcr),
665

puimonan,', anomalous origin of left coronary
arjer>’ from; report of case diag-
nosed clinically and confirmed by
necropsy (Eidlow and Mackenzie).
243

subclavian, left, right-sided aorta with atypi-
cal coarctation involving only; hy-
pertension (Master), 778

Atheromatosis in dogs following repeated intra-
vettous injections of hvdroxvccllu-
loso, 130*

Atheromatous coron.try disease of early onset
ami parallei course in twins, 403*

Atherosclerosis for coronary arteries, predilec-
tion of, 805*

Atmosphere, comfortable, rates of water and
heat loss from respiratorj' tract of
patients with congestive heart fail-
ure who were from subtropical cli-
mate and resting in (Burch), 88

.Atmospheric temperature and humidity, influ-
ence of variations in, on rates of
water and heat loss from respiralorj-
tract of patients with congestive
heart faihirc living in subtropical
climate (Burch), 190

Auricular and ventricular cavities, right, in
man. {lotcnti.al variationsof (IJcclit),
39

diastolic murmur with heart block in elderly
patients (Ryland), 579
•fibrillation in association with congestive
failure, quinidtne in treatment of,
!3r

flutter, est.abh’shed, combined use of lanato-
sidc C and rpiinidinc sulfate in abo-
lition of (Tandowsky et ah), 617
intercun’ent. cxunplote auricuiovenlricular
blfK-k and bundle branch block %vith
(de Moiini), 791

left, quanritative rocntgenographic
mi-th'x! for determination of. 405*
•st.indsriU, 123*

Auri-.'vd-Vt'entticxdar complelr. and bun-

db* bnmrh b'.<Kk with intcrcurrcnt
anrictibr flutter (de Moura), 7'JV
(ixtdA.'.'i/jpli.igcal, 267*

B

Bacterial endarteritis, acute, 673*
endocarditis, subacute, penicillin in; report
to Medical Research Council of 147
patients treated in fourteen centers
appointed by Penicillin Clinical
Trials Committee, 540*
refractor^' case of, due to VeiUonclla
S,azoge.iics clinically arrested by com-
bination of penicillin, sodium para-
aminohippuratc, and heparin
(Loewe et ai.), 327
results in treatment of, 539*
treatment of, with penicillin, 130*

Behavior of heart during manipulation, indica-
tions for removal of intracardiac
foreign bodies and (III); foreign
bodies in and in relation to thoracic
blood vessels and lieart (Harken
and ZoW), 1

Beriberi heart disease, 542*

Bicuspid aortic valve diagnosed during life,
401* ■

Bilateral pulmonary infarction and pneumo-
thorax eompliaiting hypertensive,
coronary heart disease with myo-
cardial infarction (Rogers), 519

Biloculare, cor (Bembenista), 394

Biochemical changes, abnormal, in patients
with severe, acute medical illnesses,
with and without peripheral vascu-
lar failure: mediail shock, 132*

Blood cells, human, powdered, clinical evalua-
tion of, in treatment of ulcers of
extremities associated with vascular
disorders (Anderson et al.), 754
flow, peripheral, rectal and skin tcinpcratiirc
in congestive heart failure: cfTccts
of rapid digitalization in tliis state,
811*

pulmonarj’, studies of roentgen density of
lungs in humans ns measure of, 270*
renal, decreased, edema and, in patients
with chronic congestive heart fail-
ure: evidence of “forward failure”
as primarj’’ cause of edema, 674*
velocity of, in normal pregnant women
(Manchester and Lotibe), 215
plasm.i proteins in patients with heart fail-
ure, 539*

pressure, in pulmonary artery, method fof
determining, 671*

influence of age on (Russek et a!.), 468
of hypertensive patients, efTccl of lowering,
by high spinal anesthesia on renal
function as rncasured by initlin and
diodrast clearance (V'^I); studies on
hypertension, 40S*

residual, of heart, relation between circula-
tion time and amount of (Gernandt
and Nylin). 411

coronary, in man, attempt at roentge-
nologic visualization of, 812*

SUBJECT INDEX

Blood vessels — Cont’d

thoracic, and heart, foreign bodies in and
in relation to; 111. ■ Indications for
■ removal of intracardiac foreign bod- ■
ies and behavior of heart during
manipulation (Harken and Zoll), 1 '
volume, cardiac “competence,” and exercise,
central venous pressure in relation
to, 812*

in clinical shock; IT. Extent and cause of
blood volume reduction in trau-
matic hemorrhagic and burn shock,
271*

Book reviews, 275, 409, 676, 813

Bundle branch block, complete auriculoven-
tricular block and, with intercur-
rent auricular flutter (de Moura),
794

C

Calcium, magnesium and, influence of, on pro-
prioceptive regulation of arterial
pressure, 675*

Capacity, functional, of heart, practical test for
determination of, 402*

Capillary fragilitj', increased, new drug for
treatment of: rutin, 274*

Carcinoma of esophagus, genesis of aortic per-
foration secondary to, 674*

Cardiac arrest after spinal anesthesia; report of
case with recovery, 404*
“competence,” blood volume, and exe'rcise,
central venous pressure in relation
to, 812*

enlargement in fever therapy induced by
intravenous injection of typhoid
vaccine, 271*

dyspnea, abnormalities of respiratory oattern
in patients with (Heyer), 457
failure, some observations on pathogenesis of
edema in (Reichsman and Grant),
438

output in heart failure (Suarez et al.), 339
size of children with rheumatic heart disease,
method for measuring (comparison
with cardiothoracic index): angles
of clearance, 540*
vector, construction of (Hill), 72
weight, significance of, in rats with experi-
mental hypertension, 272*

Cardio-esophageal auscultation, 267*

Cardiodynampmetry: practical test for deter-
mination of functional capacitv of
heart, 402*

Cardiopathies, congenital, new classification of,
801*

Cardiovascular defects in Selective Service

registrants (Eanes et al.), 504

, rejection rates of Selective Service regis-
• ^ trants for (Eanes et al.), 506
specific diagnostic groups of, in Selective
Service registrants (Eanes et al.),
507

rejectees, occupations of, in Selective Service
registrants (Eanes et al.), 511

821

Cardiovascular — Cont’d

rejections in relation to age in Selective Serv-
ice registrants (Eanes et al.), 510 _ ^
renal disease, its prognostic significance in
relation to hypertension and: over-
weight, 804*

responses to breathing of 100 per cent oxygen
at normal barometric pressure, 272*
syphilis and varicose veins in Selective Serv-
ice registrants (Eanes et al.), 510 -
system in anemia, with note on particular
abnormality of sickle cell anemia,'
273*

Cardite reumatica, infeccao reumatica e, ‘275
(B. Rev.)

Carotid sinus reflex, hyperactive cardioih-
hibitory, 543*

Catheterization, right heart, demonstration of
ventricular septal defect by means
of (Baldwin et al.), 152

Cavities, right auricular and ventricular, in
man, potential variations of (Hecht),
39

Children, coronarv occlusive disease in infants
and, 273*

Cineroentgenography and electrocardiography,
movements of mitro-aortic ring re-
corded simultaneously by, 270*

Circulation time and amount of residual blood
of heart, relation between (Ger-
nandt and Nylin), 411
arm-to-tongue, parenteral vitamin B as
agent for determining; Part I
(Swenson), 612

from pulmonary to systemic capillaries,
objective method for determining,
by use of oximeter, 675*

Claudication, intermittent, and vascular spasm ;

I. Is vascular spasm contributory
cause of intermittent claudication
in patients with structural disease
of arteries? 670*

Clearance, angles of: method for measuring
cardiac size of children with rheu-
matic heart disease (comparison
with cardiothoracic index), 540*

Climate, subtropical, rates of water and heat
loss from respirator}^ tract of pa-
tients with congestive heart failure
who were from and resting in fcom-
fortable atmosphere (Burch), 88

Clubbed fingers, 268*

Coagulation of blood, effect of methylxanthines
on prothrombin time and, 802*

Coarctation, atypical, right-sided aorta with,
involving only left subclavian ar-
tery; hypertension (Master), 778

of aorta, roentgenological picture of, and its
anatomical basis, 127*

Coma, fainting and, caused by oxygen lack,
circulatory changes during, 539*

Congenital cardiopathies, new classification of
801* ■

SUBJECT

INDEX

f. Kftiv., Knhire, qiiinidine in treatment of
.i!ir!(u!ar fibriM.ition in a&sociation
nith. !al*

Ki .-'t f.iilnrc. mflnenco. of variations in atnioa-
phenc t(-tn[x-raturc and hiiniidit}’ on
of water and lical lo<s from
re-pirntory tract of patients with,
liviiiv, inMihlropicalclimate (Burcli),
5 on '

rate- of water and lieat loss from respira-
tory tract of patients with, who
were from subtropical climate and
rc-tiri.e; in comfortable atmosphere
{Hiirch). 88

C'»r adipo-iim; heart block caused by fat infil-
tration of interventricular septum
(Spain and Cathcart), 659
bilocularc (Bcrnbenistal, 394
pulmonale, chronic, study of. 804*

Cornel! conferences on thcrap\’, 275 (B. Rev.)
Coronary arteries, predilection of atheroscle-
rosis for, 805*

artery, left, anomalous oripin of, from pul-
monary artery; report of case diap-
no-ed clinically and conlirmod by
nerrop-,\’ (Eidlow and Mackenzie),
243

occlusion, acute pericarditis simulating
(Coffen and Scarf), 515
ostial --tenosis and myocardial infarction,
syphilitic gummatous aortitis as
cause of (Weinberg and Bci<singcr),
665

circnlation. 269*

di'o.f'C, anoMunia and exercise tests in diag-
uO'is of (Bibrck), 689
atheromatous, of early onset and parallel
conise in twins, 403*

heart dist-a-e, hypertensive, with mxocardial
infarction, bilateral pulmonary in-
farction and pneumothorax compli-
cating (Rogers), 519
occiU'Ion in Negroes, 400*

progre— ive, with a-sociated mediastinal
tumor, pain of unu‘-ua1 duration due
to (Donovan), 786

ruxlii'tve di*-eaHC in infants
273*

and children,

sinus rhythm (-Scherf and Harris), 443
thromlwf'.is with myocardial infarction, ex-
periences with dicumarol (3,3'
nietln’hne - bis - (4 - hydroxycoii-
marin]) in treatment of (Wright), 20
Cmaruous diphtheri,!, combined sulfonamide
.ind diohtheritic niyix'arditis in
(Ore<-ne), 250

Cv.ino-i', exiv-rimental, and anoxi-mia. clTects
of .irtiudal ductus arterio-us on,
407*

1 )

Dr- vi-nsi icular s,.ji;ai. rlemonstmtion of,
hy ms.ins of rlcht heart ratheteriza-
tir>!f f Baldwin et .al,), 152

j nefiH:ts. cardiovascular, in Selective Service
registrants (Eanes ct al.), 504

ftiabetes ineliitns, relation of tobacco smoking
to arteriosclerosis obliterans in, 4G0*

Diastolic murmur, auricular, with heart block
in elderly patients (Rytand), 579

Dicumarol (3,3'niethylene-bis-[4-hydroxycon-
inarin]), experiences with, in the
treatment of coronary thrombosis
with mvocardial infarction
(Wright), 20

use of, diagnostic and therapeutic indica-
tions; serial prothrombin estima-
tions in cardiac patients, 268*

Digitalization, rapid, cfTcct.s of, in this state:

peripheral blood flow, rectal and
skin temperature in congestive
heart failure, 811*

Diodrast clearance, inulin and, effect of lower-
ing blood pressures of hypertensive
patients by high spina] anesthesia
on renal function as measured 1)>‘
(\'I); studies on hypertension, 408*

Diphtheria, cutaneous, combined sulfonamide
and diphtheritic myocarditis in
(Greene), 250

Diphtheritic myocarditis, combined sulfona-
mide and, in cutaneous diphtheria
(Greene), 250

Dorsalis pedis, palpable, and posterior tibial
pulsations, incidence of, in soldiers
(Silverman), 82

Ductus arteriosus, artificial, elTects of. on ex-
perimental evanosis and anoxemia,
407*

Dyspnea, cardiac, abnormalities of respirntoix
pattern in patients with (Ilex'er).
457

E

I'-dclna and decreased renal blood flow in pa-
tients with chronic congestive he.nri
failure: evidence of “forwatd fail-
ure” as primarv cause of edema,
674*

in cardiac failure, some observation'; on path-
ogenesis of (Reichsman and Grant).
438

Einthoven's triangle (Wilson ct al.), 277

theory of unipolar electrocardiographic
” leads, and interpretation of prcTOr-
dia! electrocardiogram (WiRon et
a!.), 277

Electrical current.s, some results of recording.

from right auricle and ventricle by
direct intraravity lead, 401*

Electrocardiogram, esophageal, in arrhythmias
and taclivcardias (Bntterworth and
Poindexter), 681

in hvpoxcniic st.iti', newer investigations on.
809*

SUBJECT INDEX 823

Electrocardiogram — Cont’d
in normal subjects, effect of meals on (Simon-
. son et al.), 202 ’

in toxemias of pregnancy, 673*
normal and pathological P-Q time of, 12,7*
precordial, in high lateral m 3 focardial in-
farction (Rosenbaum et al.), 135
interpretation of (Wilson et al.), 293
on Einthoven’s triangle, theory of unipolar
electrocardiographic leads, and in-
terpretation of (Wilson et al.), 277
T wave of, at different age levels (Suarez
and Suarez, Jr.), 480

Electrocardiograms, multiple precordial, simpli-
fied and more standardized tech-
nique for recording (Geiger and
Goerner), 163

Electrocardiographic changes occurring during
treatment with fuadin solution
(Beaser and Rodriguez-Molina),
634

during upper respirator}’ infections
(Young), 383 •

findings, clinical anah’sis of primary aytipcal
pneumonia, with discussion of, 542*
interpretation, 4''‘9 (B. Rev.)
leads, unipolar, theor}’ of, Einthoven’s tri-
angle, and interpretation of pre-
cordial electrocardiogram (Wilson
et al.), 277

manifestation, unusual, of intra-auricular
dissociation in pair of identical
twins, 128*

patterns in penetrating wounds of heart
(Noth), 713

survc}' on three hundred Negro and two hun-
dred white subjects, persistence of
juvenile pattern in precordial leads
of health}’ adult Negroes, with re-
port of (Littmann), 370
syndrome, paroxvsmal ventricular tachy-
cardia followed by (Smith), 257

Electrocardiography, 409 (B. Rev.)

following exercise, peculiar conduction dis-
turbance persisting latently after
recovery from comolete heart block
and disHosed only bv, 128*
in practice, 676 (B. Rev.)
movements of mitro-aortic ring recorded
simultaneously by cineroentgenog-
raphy and, 27<'*

Electrokardiogramm, B^itrag zur Beurteilung
des runden Oberganges von R und
ST Strecke in, 132*

Electrokymograoh for recording heart motion
utilizing the roentgenoscope, 399*

Elderly patients, auricular diastolic murmur
with heart block in (Rytand), 579

'Embolism, thrombosis and, 125*

Endarteritis, bacterial, acute, 673*

Endocardial sclerosis in infants and children,
^ 810*'

Endocarditis, bacterial, subacute, complicated
. , by pregnancy, successfully treated

with penicillin, 399*

Endocarditis, bacterial, subacute— Cont’d

refractory case of, due to VetUoneUa
gazogenes clinically arrested by
combination of penicillin, sodium
para-aminohippurate, and heparin
(Loewe et al.), 327
results in treatment of, 539*
treatment of, with penicillin, 130*

• meningococcus, 274*

Epidemiological and sociological observations,
some, incidence of rheumatic fever
and heart disease in school children
in Dublin, Georgia, with (Quinn),
,234

Esophageal electrocardiogram in arrhythmias
and tachycardias (Butter\vorth and
Poindexter), 681

Essential hypertension; renin in (Taquini and
Fasciolo), 357

Esters, synthetic, of strophanthidin, acetate,
propionate, butyrate, and benzoate,
behavior of, in man, 126*

Exercise, cardiac "competence,” blood volume,
and, central venous pressure in
relation to, 812*

tests, anoxemia and, in dia.gnosis of coronary
disease (Biorck), 689

Extremities, ulcers of, associated with vascular
disorders, clinical evaluation of
powdered human blood cells in
treatment of (Anderson et al), 754
upper, neurovascular syndrome as mani-
fested in (Pauli), 32

Extremity, lower, varicosities of, 81C*

F

Failure, cardiac, some observations on path-
ogenesis of edema in (Reichsman
and Grant), 438

heart, cardiac output in (Suarez et al.), 339

Fainting and coma caused by oxygen lack,
circulatory changes during, 539*

Fat infiltration of interventricular septum
(cor adiposum), heart block caused
by (Spain and Cathcart), 659

Fever, rheumatic, acute, effect of salicylate
on (Warren et al.), 311
and heart disease, incidence of, in school
children in Dublin, Georgia, with
some epidemiological and sociolog-
ical observations (Quinn), 234
therapy induced .by intravenous injection
of typhoid vaccine, cardiac enlarge-
ment in, 271*

Fibrillation, transient ventricular (Zimdahl and
Fulton), 117

Fingers, clubbed, 268*

Flutter, auricular, established, combined use
of lanatoside C and quinidine sul-
fate in abolition of (Tandowskv
et al.), 617

intercurrent, complete auriculoventricular
block and bundle branch block with
(de Moura), 794

824

SUBJECT INDEX

I'o-ekn \h)4u’!- in and in rtdalion to thoracic
blood vessels and heart; III. In-
dications for removal of intracardiac
foreign bodies and behavior of
heart during manipulation (Harken
and Zoll), 1

Fuadin solution, electrocardioRraphic changes
orcurrinp durinjr treatment with
(Reaser and RodriRUez-Molina).
6.14

G

Gaskdl effect, study of, 673*

Gastrointestinal tract, .syndrome of abdominal
aortic aneurysm rupturing into
(Hunt and WcHer), 571

Gazogene!:, VciUoncUa, refractory case of sub-
acute bactei'ial endocarditis dee to,
clinically arrested by combination
of penicillin, sodium para-amino-
hippurate, and heparin (Loewe
et al.), 327

Georgia. Dublin, incidence of rheumatic fever
and Iieart disease in .school children
in, with some epidemiological and
sociological observations (Quinn),
234

Glomerulonephritis, acute, purpuric mani-
festations of rheumatic fever and
(Jone.s and Moore). 529

Gummatous aortitis, syphilitic, as cause cf
coronary artery ostial stenosis and
myocardial infarction (Weinberg
and Beissinger), 665

II

Heart block, auricular diastolic murmur with.

in elderly patients (Rytand). 579
caused by fat infiltration of interventric-
ular septum (cor adiposum) (Spain
and C.athcart). 659

complete, peculiar conduction disturbance
persisting latently after recovery
from, and disclosed only b)- electro-
cardiography following e.xercise,
12S*

di'^ease, beriberi, 542*
ctironary, hypertensive, with mtocardial
infarction, bilateral pulmonary in-
farction an<l ptU'Umothorax com-
plicating (Rogers). 519
incidence of rheumatic fever and, in school
children^ in Dublin, Gi'orgia, with
some <-indemia!ogir.\! and st>ciolnei'
cal oij'.erv.ation,' fOiiinn). 2.34
rheumatic, icro-*- v.ascidaritv of mitral
v.dve ,as -tigrnn of. 131*
rheumatic fever and. in Xorth .Xfrican
and Metliterranean '1‘heater of
O'H-r.ations, I'nited States .-\rmv
(Bbfxi), 54S

v.alvnlai. effect of salicvl.ue on (Warren
et nl.), 320

tKUterns in pinetratin.e
of (Noth), 713

Heart — Cont’d

failure, blood plasma proteins in patients
with,' 539*

cardiac output in (Suarez et al.), 339
congestive, influence of variations in at mes-
phcric temperature and humidity
on rates of water and heat loss
from respiratory tract of patients
with, living in subtropical climate
(Burch), 190

low-sodium diet and free fluid intake
in treatment of, 4C4*
peripheral blood flow, rectal and skin
temperature in; effects of rapid
digitalization in this state, 811*
proteinuria of effort and its significance
in diagnosis of, 8(,-2*
rates of water and heat loss from res-
piratory tract of patients with,
who were from subtropical climate
and resting in comfortable atmos-
phere (Burch), 88
fluids in, 803*

foreign bodies in and in relation to thoracic
blood vessels and: III. Indications
for removal of intracardiac foreign
bodies and behavior of heart during
manipulation (Harken and Zoll), 1
functional capacity of, practical test for
determination of, 402*
hypertrophy of, of unknown etiology in
young adults: report of four cases
witli autopsies (Norris and Pole),
599

in primarv svstcinic amvloidosis (Lindsav),
419 ■

motion, electrokymograph for recording.

utilizing roentgcnoscope, 399*
relation between circulation time and amount
of residual blood of (Gernandt
and Nylin), 41 1

riglil, catheterization, demonstration of ven-
tricular septal defect by means of
(Baldwin et al.), 152

stimulating action of acetylcholine on, 4(8*
weight; II. Effect of tuberculosis on lieait
weight, 674*

lle.it loss, wafer and, from respiratory tract
of patients with congestive heart
failure living in subtropical climate,
influenct' of variations in atmos-
pheric temperature and humidity
on (Burch), 190

water and, loss, rates of, from re.spirntory
tract of patient.s with conge'-tive
heart failure wlio were from sub-
tropical climate .inel ri'stinc in
comfortable atmosphere (Burch), 8H
Heparin, penicillin, .sodium pnra-aniinohip-
purate, and, refractory ca«e of
subacute bacterial endocarflitis flue
to Veillonefl/i pnzozene.! clinically
arre.sted by combinniion of (Lotwe
et a!.), .327

1 therapy in .icute venous thrombosis, 4t'(-*

825

SUBJECT

Human blood cells, powdered, clinical evalua-
tion of, in treatment of ulcers of
extremities associated with vascular
disorders (Anderson et al.), 754
Humidity, influence of variations in atmos-
pheric temperature and, on rates
of water and heat loss from respira-
tory tract of patients with conges-
tive heart failure living in sub-
tropical climate (Burch), 190
Hydroxycellulose, atheromatosis in dogs fol-
lowing repeated intravenous injec-
tions of, 130*

Hypertension and cardiovascular renal disease.

its prognostic significance in rela-
tion to: overweight, 8C4*
arterial, relation of arterial pulse pressure
to arteriovenous oxygen difference,
especially in, 126*

selection of patients with, for treatment
bv repeated injections of pitressin,

8r6*

essential, analysis of surgical failures and
fatalities following thoracolumbar
sympathectomv for, 8f5*

■ renin in (Taquini and Fasciolo), 357
splenorenopexy in, 407*
experimental, significance of cardiac weight
in rats with, 272*

right-sided aorta with atypical coarctation
involving onlv left subclavian artery
(Master). 778

some effects of rice diet treatment of kidney
disease and, 8P8*

studies on; VI. Effect of lowering blood
pressures of hypertensive patients
by high spinal anesthesia on renal
function as measured by inulin and
diodrast clearance, 4C8*
unilateral renal, present status of, 130*
Hypertensive, coronary heart disease with
myocardial infarction, bilateral pul-
monary infarction and pneumo-
thorax complicating (Rogers), 519
patient, selection of, for svmpathectomv,
267* ;

Hypertrophy of heart of unknown etiology in
young adults: report of four cases
with autopsies (Norris and Pote),
599

Hypothyroidsim and mild my.xedema from
thiocyanate intoxication, 811*
Hypoxemic state, newer investigations on elec-
trodiogram in, 809*

• I

Iliac veins, ligation of inferior vena cava or;

report of 136 operations, 807*
Infant, paroxysmal nodal tachycardia in, 808*
Infants and children, coronary occlusive dis-
ease in, 273*

Infarction, high lateral myocardial, precordial
electrocardiogram in (Rosenbaum
et al.), 135

INDEX

Infarction — Cont’d

myocardial, bilateral pulmcnary infarction
and pneumothorax complicating
hj'pertensive, coronary heart dis-
ease with (Rogers), 519
e.xperiences with dicrmarol (3,3' methy-
Iene-bis-[4-hydroxycoumarin]) in
treatment of coronary thrombosis
with (Wright), 20

syphilitic gummatous aortitis as cause of
coronary artery ostial stenosis and
(Weinberg and Beissinger), 665
pulmonary, bilateral, and pneumothorax
complicating hypertensive, coronary
heart disease with myocardial in-
farction (Rogers), 519

Infeccao reumatica e cardite reumatica, 275
(B. Rev.)

Infections, respiratory, upper, electrocardio-
graphic changes occurring during
(Young), 383

Inflammations, scarifying, calcifying, of peri-
cardial sac, and results of operative
management, on, 8C9*

Ingestion of large amounts of sodium chloride,
effects of, on arterial and venous
pressures of normal subjects (Grant
and Reichsman), 7C4

Innervation of veins; its role in pain, veno-
spasm, and collateral circulation,
671*

Insufficiency, tricuspid, parasternal leads in
(Ellis and Brown), 364

Interventricular septum (cor adiposum), heart
block caused by fat infiltration of
(Spain and Cathcart), 659

Intra-auricular dissociation in pair of identical
twins, unusual electrocardiographic
manifestation of, 128*

Intracardiac foreign bodies, indications for
removal of, and behavior of heart
during manipulation (III); foreign
bodies in and in relation to thoracic
blood vessels and heart (Harken
and Zoll), 1

Inulin and diodrast clearance, effect of lower-
ing blood pressures of hypertensive
patients by high spinal anesthesia
on renal function as measured by
(VI); studies on hypertension, 4G8*

J

Juvenile pattern, persistence of, in precordial
leads of healthy adult Negroes,
with report of electrocardiographic
survey on three hundred Negro and
two hundred white subjects (I.itt-
mann), 370

K

Kidney disease and hypertension, some effects
of rice diet treatment of, 808*

.subject index

S2i-

Ljn.nO'i.ic C nnd uuiniHinc .^ulfntr, combineti j
U'-t' of. in nbolition of c.'tablishcd
auricular flutter (Tandow.^ky ot ab),
617

intrncavity direct, some re.'^ults of rc-
ror<iine electrical currents from
rittht auricle and ventricle by,
4i)i*

l.-.td-, elcctrocardiofirapbic, unipolar, theory
of. Einthoven's trianele, and inter-
pretation of prccordial electrocar-
diotiram (Wil.son et ab), 277
para-ternab in tricuspid insufiiciency (Ellis
and Brown). .164

prccordial. of healthy adult Negroes, per-
si.sience of pivenile pattern in, with
report of electrocardiographic sur-
ve\- on three hundred Negro and
two hundred white subjects (Litt-
mann). 370

Left coronarj- arter\-, anomalous origin of.

from inilnionary artcrv; report of
ra-e diagnosed clinically and con-
t'lrmeil bv necropsy (Eidlow and
Mackenr.ie), 243
betters. 307

Life expectancy in angina pectoris, 269*
bumi)ai -vmpathectomv for chronic leg ulcers.
405*

Lupus erythematosis disseminatus and related
fli'-eases, pathogenetic studie.s on,
126*

bviuphedema of arm, post-onerat ivo, preven-
tioit .ind treatment of, 672*

M

Magm-^iiim and calcium, influence of. t)n pro-
prioceptive rt-gulaiion of arterial
pre.ssure. 675*

Manipulation, indications for removal of intra-
cardiac foreign bodies and behavior
Ilf heart during (III); foreign bodie.s
in and iu relation to thoracic blood
ve.-seK and heart (Harken and
Zoin. 1

Mf-rtb. eitett of, on eliH-trocnrdiogiam in normal
siib-iects (Simon-on et ab), 2(!2
^Mcdi.astinal ttuunr. a- sociatid, pain of unusual
fluration due to nroeres-ive coro-
nary wlnsirin with (Donovan). 786
Mtdical and surgieM treatment of trench foot
(Abramson et .ab), 61

«his.'k; abnorinii biochemir.d changt-s in
iK'tii'nts with M-vere, tirute medical
ilim— (•', vdih and witluiiit peri-
pltCMl v.i-ru!ar failure, 132*
tb-’ikia-j.tnean. North Afnn.in and. Theater
u: Dprr.ith.n-, Uniti-d States Armv,
Hit fervr and rhi-iimatir

heaft in fHlnnil). .l-IS

3,3'Methylenc-bis-(4-hydroxycoumarin). expe-
riences with, in treatment of coro-
nary thrombosis with myocardial
infarction (Wright), 20

Methylxanthines, effect of, on prothrombin
time and coagulation of blood, S02*
Mitral valve, gross vascularity of, a.s stigma
of rheumatic heart disease, 131*
Mitro-aortic ring, movements of, reconietl
simultaneously by cineroentgenog-
raphy and electrocardiography, 270*
Multiple prccordial electrocardiograms, sim-
plified and more standardised tech-
nique for recording (Geiger and
Goerncr). 163

Murmur, diastolic, auricular, with heart block
in elderly patients (Rytand), 579
Myocardial infarction, bilateral pulmonary
infarction and pneumothorax com-
plicating hypertensive, coronary
heart disease with (Ropers), 519
experiences with dicumarol (.b3''nu'thy-
!cne-bis-(4-hx droxycoiimarin]) in
treatment of coronary thrombosis
with (Wright), 20

high lateral, prccordial electrocardiogram
in (Rosenbaum et ab), 135
syphilitic gummatous aortitis as cause of
coronar\’ artery ostial stenosis and
(Weinberg and Reissingcr), 665
Myocartlii. annloidosis, 127*

Myocarditis, combined sulfonamide and diph-
theritic, in cutaneous diphtheria
(Greene), 250

Myxedema, mild, hypothvroidisni and, from
thiocyanate intoxication. 811*

N

Negroes, adult, healthy, persistence of juvenile
pattern in precordial leads of, with
report of electrocardiographic sur-
vey on three hundred Negro and
two himflred white snbject.s (bitt-
mann), 37f'

roronarv occlusion in, 40f *

Neurocircnlatory asthenia, effect of exercise
on sohiiers with, 671*

svndrome (neiirfjrircnlatorv asthenia), in
s-oldier.s, 126*

Neurovascular syndrome as manifested in
upper extremities (Pauli), 32
Newborn, rubella iu jiriynancy causing mnl-
form.Uion- in. 131 *

Nodal tachycardia, paroxy.sninl, plasma con-
cent rations of quinidine with par-
ticular refereiire to t her.Tpeiiticallv
effective level-' in two <.'ues of
(Dcb-veit and Poinde.vter), 6*i7
Normal prc-gnnnf womeit, v.-l(y:ity o*" blood
flow in (Manchester and boubc).
215

-nbject,'. I ffect of meals on el'-ctrfrcardiogr.ani
in (Simon-on et .'ib). 2f’2

SUBJECT

Normal subjects — Cont’d

effects of ingestion of larre amounts of
sodium chloride on arterial and
venous pressures of (Grant and
Rcichsman), 704

North African and Mediterranean Theater
of Operations, United States Army,
rheumatic fever and rheumatic
heart disease in (Bland), 545

O

Obliteration, venous, collateral channels in,

' 807*

Occlusion, coronary artery, acute nericarditis
simulating: (Coffen and Scarf), 515
progressive, with associated mediastinal
tumor, pain of unusual duration,
due to (Donovan), 786

O.-thostatic paroxysmal ventricular tachycardia
(Peters and Penner), 645

Ostial stenosis, coronary arterv, and mj'ocardial
infarction, syphilitic gummatous
aortitis as cause of (Weinberg and
Beissinger), 665

Output, cardiac, in heart failure (Suarez et ah).
339

Overweight; its prognostic significance in rela-
tion to hypertension and cardio-
vascular renal disease, 804*

Oximeter, objective method for determining
circulation time- from pulmonary
to systemic capillaries by use of,
675*

Oxygen difference, arteriovenous, relation of
arterial pulse pressure to, especially
in arterial hypertension, 126*

100 per cent, cardiovascular responses to
breathing of, at normal barometric
pressure, 272*

P

Pain of unusual duration due to progressive
coronary occlusion with associated
mediastinal tumor (Donovan), 786

Palpable dorsalis pedis and posterior tibial
pulsations, incidence of, in soldiers
(Silverman), 82

Para-aminohippurate, sodium, penicillin, and
heparin, refractory case of subacute
■ bacterial endocarditis due to Veil-
lonella gazogenes clinically arrested
by combination of (Loewe et ah),
327

Parasternal leads in tricuspid insufficiency
(Ellis and Brown), 364

Parenteral vitamin B as agent for determining
arm-to-tongue circulation time;
Part I (Swenson), 612

Paroxysmal nodal tachycardia, plasma con-
centrations of quinidine with par-
ticular reference to therapeutically
effective levels in two cases of
(Delevett and Poindexter), 697

INDEX 827 .

Paroxysmal — Cont’d

ventricular tachycardia followed by electro-
cardiographic syndrome (Smith),
257 .

orthostatic (Peters and Penner), 645

Pathogenesis of edema in cardiac failure, some
observations on (Reichsman and
Grant), 438

Patterns, electrocardiographic, in penetrating
wounds of heart (Noth), 713

Pedis, palpable dorsalis, and posterior tibial
pulsations, incidence of, in soldiers
(Silverman), 82

Penicillin in subacute bacterial endocarditis;

report to Medical Research Council
of 147 patients treated in fourteen
centers appointed by Penicillin
Clinical Trials Committee, 540*
observations of treatment of scarlet fever
with, 132*

sodium para-aminohippurate, and heparin,
refractory case of subacute bacterial
endocarditis due to Veillonella
gazogenes clinically arrested by
combination of (Loewe et ah), 327

subacute bacterial endocarditis complicated
by pregnancy, successfully treated
with, 399*

treatment of bacterial endocarditis with,
130*

Pericardial sac, on calicifying, scarifying in-
flammations of, and results of;
operative management, 809*
Pericarditis, acute, in young adults (Nay and
Boyer), 222 ^ ,

simulating coronary arteiy" occlusion (Cof-
fen and Scarf), 515
Peripheral arterial diseases, 125*
Phonocardiographie, auscultation collective
(acoustique — technique — clinique),
676 (B. Rev.)

Pitressin, selection of patients with arterial
hypertension for treatment by
repeated injections of, 806*

Plasma concentrations of quinidine with par-
ticular reference to therapeutically
effective levels in two cases of par-
oxysmal nodal tachycardia (Dele-
vett and Poindexter), 697
Pneumonia, atypical, primary, clinical analysis
of, with discussion of electro-
cardiographic findings, 542*
Pneumonitis, non-suppurative post-strepto-
coccic (rheumatic), 541*
occurring in rheumatic fever, 807*
Pneumothorax, bilateral pulmonary infarction
and, complicating hypertensive,
coronary' heart disease with myo-
cardial infarction (Rogers), 519
Posterior tibial pulsations, incidence of palpa-
ble dorsalis pedis and, in soldiers
(Silverman), 82

SUBJECT INDEX

S’ib'

Poff-ntia! variations of right auricular and i
r-entricuiar cavities in man (Hechl), i
V) i

P-u time, nurinal and pathological, of electro- j
cardiogram, 127* I

ricioniial electrocardiogram in high lateral j
myiKtarfiial infarction (Rosenbaum !
et a!.). 135 I

interpretation of (Wilson et ah), 293 I

on Einthoven’s triangle, theory of unipolar 1
elect rocarriiographic leads and inter- }
pretation of (Wilson et ah), 277 !
r wave of, at different age levels (Suarez j
and Su.irez, Jr.), 480 j

electrocardiograms, multiple, simplified and i
more standardized technique for j
recording (Geiger and Goerner), 163 i
le.ids of healthy adult Negroes, persistence i
of juvenile pattern in, with report |
of electrocardiographic survey on '
three hundred Negro and two hun-
dred white subjects (Littmann), I
370 ;

Pregn.incv, electrocardiogram in toxemias of,
673* _ f

rubella in, causing mtilformations in new- .

born. 131* ’

subacute bacterial endocarditis complicated 1
by, successfully treated with peni- j
cillin, 399*

women, normal, velocity of blood flow in )
(Manchester and Loube), 215 '

Ptessurc, intravascular jincl e.xtra vascular, in
Valsalva's c.xperiment, 801* i

Pressures, arterial and venous, of normal !

subjects, elfcas of ingestion of j
large amounts of sodium chloride i
on (Grant and Reichstnan), 704
Procaine, intravenous, tre.atment of acute .

arrhvthmias fluring anesthesia by, i
270 * ;

Proteinuria of effort and its significance in ,
diagnosis of congestive heart fail- '
urc, 802* j

Prothrombin estimations, serial, in airdiac |
patients; diagnostic and therapeutic '
indications, use of dicumarol, 268* j
tiu'.e and coagulation of blood, effect of |
rncthylxanthincs on, 802* >

Pulmonary artery, anomalous origin of left '
coronary artery from;' report of
cjise diagnosed clinically and con- I
firmed by necrop.sy (Eicllow and ’
Mackenzie), 243 1

nu'thiHl for determining blood pressure
in, 671* ’ i

!hmn5bo.ingiitis of pulmonary vessels '
as'Txri.ated with ani-urvsm of; reixrrt ■
of ra«»-, 809*

infarction, bilater.xl. anti pneumothorax
Complicating hyjKTtensive, coronarv ‘
In-.-.rt di=f.i''e with invficr.rfiial in-
farmion tRrtgvrt), 519

Pub.-. t ■•JO*., palpable tl«r«.s!is {wflis ami jw-tcrior
liblth inrhleme of, in f.o!dicrs ’
fSiKrrm.m). 82

pulse pressure, arterial, relation of, to arterio-
venous oxygen difference, espe-
cially in arterial hypertension, 1 26*

Purpuric manifestations of rheumatic fever
and acute glomerulonephritis (Jones
and Moore), 529

Q

QRS complex configurations in WolfT-Parkin-
son-White syndrome, notes on
similarity of (Burch and Kimball),
560

Quinidine in treatment of auricular fibrillation
in association with congestive fail-
ure. 131*

plasma concentrations of. with particular
reference to therapeutically effec-
tive levels in two cases of paroxys-
mal nodal tachycardia (Delevett
and Poindexter), 697

sulfate, combined use of lanatoside C and.

in abolition of established auricular
flutter (Tandowsky et al.), 617

R

R und ST Strccke in

Beilrag zur •' ■■■■v.' 1 '■ :

ganges von, 132*

Reconditioning program for patients with
trench foot (Abramson cl al.), 67

Recording multiple precordial electrocardio-
grams, simplified and more stand-
ardized technique for (Geiger and
Goerner), 163

Renal hypertension, unilateral, present status
of, 130*

Renin in essential hypertension (Taquini and
Fasciolo), 357

Residual blood of heart, relation between
circulation time and amount of
(Gernandt and Nylin). 411

Respiratory infections, upper, electrocardio-
graphic changes occurring during
(V oting), 383

pattern, abnormalities of, in patients with
cardiac dyspnea (Hcyer), 457
tract of p.atients with congestive heart
failure living in subtropical climate,
influence of variations in atinos-
phcric lemperatiirc and humidity
on rates of w.iterand heat loss from
(Burch). 190

of patients with congestive heart f.aihire
who ^vcrt^ from subtropical climate
and resting in comfortaldc atmos-
phere, rates of water and heat loss
from (Burch). 8.S

Reumatica. rardite, infeccan reiimatic.t e, 275
(H. Rev.) .

829

SUBJECT

Rheumatic fev'r, acute, effect of salicylate on
(Warren et al.), 311

and acute glomerulonephritis, purpuric
manifestations of (Jones and
Moore), 529

and heart disease, incidence of, in school
children in Dublin, Georgia, with
some epidemiological and sociolog-
ical observations (Quinn), 234
and rheumatic heart disease in North
African and Mediterranean Theater
of Operations, United States Army
(Bland), 545

and rheumatoid arthritis, value of Sper-
ansky’s method of spinal pumping
in treatment of, 129*

in Naval enlisted personnel; III. Physi-
ologic and toxic effects of intensive
salicylate therapy in acute cases,
401*

pneumonitis occurring in, 807*
treatment of, by roentgen ray irradiation,
670*

heart disease, gross vascularity of mitral
valve as stigma of, 131*
method for measuring cardiac size of
children with (comparison with
cardiothoracic index); angles of
clearance, 540*

rheumatic fever and, in North African
and Mediterranean Theater of
, Operations, United States Army

(Bland), 545

pneumonitis, non-suppurative post-strepto-
coccic, 541*

Rheumatoid arthritis, value of Speransky’s
method of spinal pumping in treat-
ment of rheumatic fever and, 129*

Rh>nhm, sinus, coronary (Scherf and Harris),
443

Rice diet treatment of kidney disease and
hypertension, some effects of, 808*

Right heart catheterization, demonstration of
ventricular septal defect by means
of (Baldwin et al.), 152

Roentgen density of lungs, study of, in humans
as measure of pulmonary blood
flow, 270*

ray irradiation, treatment of rheumatic
fever by, 670*

Roentgenographic method, quantitative, for
determination of left auricular size,
405*

Roentgenologic visualization of coronary blood
vessels in man, an attempt at,
812*

Rubella in pregnancy causing malformations
in newborn, 131*

Rupture of aotric valves due to effort, 273*

Rutin; new drug for treatment of increased
= capillary fragility, 274*

INDEX

S

Salicylate, effect of, on acute rheumatic fever
(Warren et al.), 311
on fever (Warren et al.), 318
on pericarditis (Warren et al.), 322
on polycyclic attacks (Warren et al.), 319
on P-R interval (Warren et al.), 323
on sedimentation rate (Warren et al.), 315
on valvular heart disease (Warren et al.),
320

therapy, intensive, physiologic and toxic
effects of, in acute cases (III);
rheumatic fever in Naval enlisted
personnel, 401*

toxicity: probable mechanism of its action,
272*

Saline solution, hypertonic, circulatory changes
following injection of; application
to study of angina pectoris, 129*

Scarlet fever, observations on treatment of,
with penicillin, 132*

School children in Dublin, Georgia, inci-
dence of rheumatic fever and heart
disease in, with some epidemio-
logical and sociological observations
(Quinn), 234

Sclerosis, endocardial, in infants and children,
810*

vascular, peripheral, sympathectomy in,
802*

Sedimentation rate, effect of salicylate on
(Warren et al.), 315

Selective Service registrants, cardiovascular
defects in (Eanes et al.), 504

Septal defect, ventricular, demonstration' of,
by means of right heart catheter-
ization (Baldwin et al.), 152

Sickle cell anemia, cardiovascular system in
anemia, with note on particular
abnormality of, 273*

Sinus reflex, carotid, hyperactive cardioin-
hibitory, 543*

rhythm, coronary (Scherf and Harris), 443

Shock, clinical, blood volume in; II. Extent
and rause of blood volume reduc-
tion in traumatic hemorrhagic and
burn shock, 271*

concentrated human albumin in treatment
of, 672*

medical: abnormal biochemical changes in
patients with severe, acute medical
illnesses, with and without peri-
pheral vascular failure, 132*

Smoking, tobacco, relation of, to arteri-
osclerosis obliterans in diabetes
mellitus, 400*

Sociological observations, some epidemio-
logical and, incidence of rheumatic
fever and heart disease in school
children in Dublin, Georgia, with
(Quinn), 234

830

SUBJECT INDEX

Sodium Chloride, effects of ingestion of large
amounts of, on arterial and venous
■pressures of normal subjects (Grant
and Reichsman), 70-f

low-, diet and free fluid intake in treatment
of congestive heart failure, 404*

para-aminohippurate, penicillin, and heparin,
refractorj'^ case of subacute bac-
terial endocarditis due to Veil-
lonella gazogeiies clinically arrested
by combination of (Loewe et al.),
327

Soldiers, incidence of palpable dorsalis pedis
and posterior tibial puslations in
(Silverman), 82

Spinal anesthesia, cardiac arrest after; report
of case with recover^’, 404* i

high, effect of lowering blood pressures of
hypertensive patients by, on renal
function as measured by inulin and
diodrasl clearance (VJ): studies on
hypertension, 408*

pumping, value of Speransky’s method of,
in treatment of rheumatic fever and
rheumatoid arthritis, 129*
Splcnorenopexy in essential hypertension, 407*
ST Strecke, Beitrag zur Beurteilung des
runden Oberganges von R und, in
Elect rokardiogra mm, 132*

Stenosis, aortic, due to calcified, syphilitic
valvulitis, 403*

ostial, coronary' arter>', and myocardial
infarction, syphilitic gummatous
aortitis as ctiuse of (Weinberg and
Bcissingcr), 665 ’ j

Strophanthidin, behavior of synthetic esters
of. acetate, propionate, butyrate, i
and benzoate in man, 126* I

Subclavian artery, left, right-sided aorta with i
atypiail coarctation involving only; 1
hypertension (.Master), 778 j

Subtropical climate, influence of variations j
in atmospheric temperature and i
humidity on rates of water and j
heat loss from respiratory tract of ■
patients with congestive heart '
failure living in (Burch), 190 i

rates of water and heat loss from respira- '
lory tract of patients with conges- i
live heart failure who were from <
and resting in comfortable atmos- !
phere (Burch), 88

S’.ilfonamicle and diphtheritic myocarditis.

combined, in cutaneous diphtheria i
(Greene), 250

.Surgierd. medical and, treatment of trench
fwn (Abram'^in ct al.), 61

Svmjrtthcctomy in peripheral vasenktr sclcr-
S02‘

luntlxir. for chronic leg ulcers. -SOS

Sympathetic blocks, repeated; limitation and
value, 407*

Syndrome, electrocardiographic, paro.xysmnl
ventricular tachycardia followed by
(Smith), 257

neurocirculatorc’ syndrome (neurocirculatory
asthenia) in soldiers, 126*
neurovascular, as manifested in upper ex-
tremities (Pauli), 32

of abdominal aortic aneurysm rupturing
into gastrointestinal tract (Hunt
and Weller), 571

Wolff-Parkinson-While (Littmann and Tar-
nower), 100

notes on similarity of QRS complc.v con-
figurations in (Burch and Kimball),
560

Synthetic esters of strophanthidin, acetate,
propionate, butyrate, and benzoate,
behavior of, in man, 126*

Syphilitic gummatous aortitis as cause of
coronary artery ostial stenosis and
myocardial infarction (Weinberg
and Bcissingcr), 665

Systemic amyloidosis, primary, heart in
(Lindsay), -119

T

T wjivc of precordial electrocardiogram at
different age levels (Suilrcz and
Suarez, Jr.), 480

Tachyciirdia, nodal, paro-vysmal, in infant,
808*

plasma concentrations of quinidine with
particular reference to therapeu-
tically effective levels in two cases
of (Delevett and Poindexter), 697
ventricular, paroxysmal, followed by electro-
cardiographic syndrome (Smith),
257

orthostatic (Peters and Penner), 645

Tachycardias, esophageal electrocardiogram in
arrhythmias and (Butterwortli and
Poinde.xtcr), 681

Technique, simplified and more standanlized,
for recording multiple prccordial
electrocardiograms (Geiger and
Goerncr), 163

Temperature, atmospheric, and humidity.

influence of variations in. on rate.'’
of water and heat loss from respira-
tory tract of patients with conges-
tive heart - failure living in sub-
tropical climate (Burch), 190
rectal and skin, peripheral blood flow, in
congestive heart failure: effects of
rapid digitalization in this state,
811*

Temf)or.al arteritis; generalized v.ascular dis-
ease, 406*

tf-Iertinn t.f hj’p'-nt-n'-ivc patients for, 267* ;
thoraodsirabar, _ for {-sscntial hyjrt'rtension, ,
.anaiyrii of surgical failures and !
fat.djtie'S fononint* 1

Tc.stosierone in angina pectoris, 806*

Therapy, Cornell conference.s on, 275 (B. Rev.)
Thiocyanate intoxication, hyfwthyroiflism and
mild niy.vederna from, 811’

SUBJECT

Thiouracil treatment of angina pectoris, dis-
advantages of (DiP.alma and Ma-
Govern), 494

Thoracic aorta, descending, aneurysm of
(Loewenberg and Baer), 653
blood vessels and heart, foreign bodies
in and in relation to; III. Indica-
tions for removal of intracardiac
foreign bodies and behavior of
heart during manipulation (Harken
and Zoll), 1

Thoracolumbar sympathectomy for essential
hypertension, analysis of surgical
failures and fatalities following, 805*

Thromboangiitis of pulmonary vessels asso-
ciated with aneurysm of pulmonary
artery: report of case, 809*

Thrombosis and embolism, 125*

coronarjf, with myocardial infarction, ex-
periences with dicumarol (3,3'meth-
ylene-bis-[4-hydroxycoumarinl) in
treatment of (Wright), 20
slowly progressive occlusive, of abdominal
portion of aorta, 127*
venous, acute, heparin therapy in, 400*

Tibial pulsations, posterior,, incidence of
palpable dorsalis pedis and, in
soldiers (Silverman), 82

Time, circulation, and amount of residual blood
of heart, relation between (Ger-
nandt and Nylin), 411

ToxicitJ^ salicylate: probable mechanism of
its action, 272*

Tract, respiratory, of patients with congestive
heart failure living in subtropical
climate, influence of variations
in atmospheric temperature and
humidity on rates of water and heat
loss from (Burch), 190

Transient ventricular fibrillation (Zimdahl
and Fulton), 117

Traumatic aneurysms of. extremities, 407*

Treatment, thiouracil, of angina pectoris, dis-
advantages of (DiPalma and Ma-
Govern), 494

Trench foot, clinical picture and treatment of
later stage of (Abramson et al.), 52 .

Tricuspid insufficiency, parasternal leads in
(Ellis and Brown), 364

Tuberculosis, effect of, on heart weight (II)’-
heart weight, 674*

Tumor, mediastinal, associated, pain of un- i
usual duration due to progressive
coronary occlusion with (Donovan)
786 j

Typhoid vaccine, cardiac enlargement in fever j
therapy induced by intravenous '
injection of, 271* . '

u

• Ulcers, leg, chronic, lumbar sympathectomy
for, 405*

INDEX . 831 .

Ulcers — Cont'd

of extremities associated with vascular dis-
orders, clinical evaluation of pow-
dered human blood cells in treat-,
ment of (Anderson et al.), 754

Unilateral renal hypertension, present status
of, 130*

Unipolar electrocardiographic leads, theory of, '
Einthoven’s triangle, and interpre-
tation of ■ precordial electrocardio- .
gram (Wilson et al.), 277 :

leads (Wilson et al.), 282

United States Army, rheumatic fever and :

rheumatic heart disease in North
African and Mediterranean Theater
of Operations (Bland), 545

Upper extremities, neurovascular syndrome as
manifested in (Pauli), 32

V

Valsalva's experiment, intravascular and ex-
travascular pressure in, 801*

Valvulitisj syphilitic, calcified, aortic stenosis
due to, 403*

Variations, potential, of right auricular and
ventricular cavities in man (Hecht), -
39

Varicose veins, cure of, 1 25*

Varicosities of lower extremity, 810*

Vascular disorders, clinical evaluation of ’
powdered human blood cells in '
treatment of ulcers of extremities
associated with (Anderson et al.),
754

failure, peripheral, abnormal biochemical
changes in patients with severe,
acute medical illnesses with and
without: medical shock, 132*
spasm, intermittent claudication and; I. Is
vascular spasm contributory cause
, of intermittent claudication in
patients with structural disease of
arteries? 670*

Vascularization of aorta, studies on; I. Vascu-
larization of aorta in normal dog
(Schlichter), 770

Vector cardiac, construction of (Hill), 72

Veillonella gazogenes, refractory' case of suba-
cute bacterial endocarditis due to,
clinically arrested by combination
of penicillin, sodium para-aminohip-
purate, and heparin (Loewe et al.),
327

Veins, innervation of: its role in pain, veno-
spasm, and collateral circulation.
671* . .

varicose, cure of, 125*

Velocity of blood flow in normal pregnant
women (Manchester and Loube),
215 -'

Vena cava, inferior, or iliac veins, ligation of;
report of 136 operations, 807*

SUBJECT IN’DEX

s :’,2

'.'i-nrti!*-, arroriai and, pressures of normal
subjects. efTects of ingestion of
large amounts of sodium chloride
on (Grant and Rcichsman), 704
//olitcraf ion, collateral channels in, S07*
j.!cssure. clinical studies on; 1. Technique:
venous pressure in normal individ-
uals. S04«

pulse and its graphic recording, 676 (B. Rev.)
\'cnt ricul.tr ancutA-sm, longevity with; report
of case with survival period of
fifteen years, 402*

cavities, right auricular and, in man, poten-
tial variations of (Hccht), 39
fibrilhnion, transient (Zimdahl and Fulton),
117

septal defect, demonstration of, by means
of right heart cjitlietcrization (Bald-
win cl ah), 152

tachycardia, paroxysmal, followed by elec-
trocardiographic svndrome (Smith),
257 _

orthostatic (Peters and Penner), 645
\it;imin B, parenteral, as agent for deter-
mining arni-to-tonguc circulation
lime; Part 1 (.Swenson), 612

W

Water and licat los.s from respiratory tract of
patients with congestive heart fail-
ure living in subtropical climate,
influence of variations in atmos-
pheric temperature and humidity
on (Burch), 190

Water and heal lo.ss — Cont'd

rates of, from respiratory tract of
patients with congestive heart fail-** •
lire who were from subtropical
climate and resting in comfortable
atmosphere (Burch), S8

White subjects, two hundred, three hundred
Negro and, persistence of juvenile
pattern in precordial leads of
healthy adult Negroes, with report
of electrocardiographic survey on
(Littmann), 370

WolfT- Parkinson-White syndrome (Littmann
and Tarnower), 100

notes on similarity of QRS complex con-
figurations in (Burch and Kim-
ball), 560

Wounds, penetrating, of heart, electrocardio-
graphic patterns in (Noth), -713

Y

Young adults, hypertrophy of heart of un-
known etiology in: report of four
cases with aulopjiics (Norris and
Pole), 599